Browsing by Subject "CARDIOVASCULAR RISK"

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  • Tukiainen, Taru; Pirinen, Matti; Sarin, Antti-Pekka; Ladenvall, Claes; Kettunen, Johannes; Lehtimaeki, Terho; Lokki, Marja-Liisa; Perola, Markus; Sinisalo, Juha; Vlachopoulou, Efthymia; Eriksson, Johan G.; Groop, Leif; Jula, Antti; Jaervelin, Marjo-Riitta; Raitakari, Olli T.; Salomaa, Veikko; Ripatti, Samuli (2014)
  • Mantyselka, Pekka; Niskanen, Leo; Kautiainen, Hannu; Saltevo, Juha; Wurtz, Peter; Soininen, Pasi; Kangas, Antti J.; Ala-Korpela, Mika; Vanhala, Mauno (2014)
  • Nuotio, Joel; Vahamurto, Lauri; Pahkala, Katja; Magnussen, Costan G.; Hutri-Kahonen, Nina; Kahonen, Mika; Laitinen, Tomi; Taittonen, Leena; Tossavainen, Paivi; Lehtimaki, Terho; Jokinen, Eero; Viikari, Jorma S. A.; Raitakari, Olli; Juonala, Markus (2019)
    Aims: Disparity in cardiovascular disease (CVD) mortality and risk factor levels between urban and rural regions has been confirmed worldwide. The aim of this study was to examine how living in different community types (urban-rural) in childhood and adulthood are related to cardiovascular risk factors and surrogate markers of CVD such as carotid intima-media thickness (IMT) and left ventricular mass (LVM). Methods: The study population comprised 2903 participants (54.1% female, mean age 10.5 years in 1980) of the Cardiovascular Risk in Young Finns Study who had been clinically examined in 1980 (age 3-18 years) and had participated in at least one adult follow-up (2001-2011). Results: In adulthood, urban residents had lower systolic blood pressure (-1 mmHg), LDL-cholesterol (-0.05 mmol/l), lower body mass index (-1.0 kg/m(2)) and glycosylated haemoglobin levels (-0.05 mmol/mol), and lower prevalence of metabolic syndrome (19.9 v. 23.7%) than their rural counterparts. In addition, participants continuously living in urban areas had significantly lower IMT (-0.01 mm), LVM (1.59 g/m(2.7)) and pulse wave velocity (-0.22 m/s) and higher carotid artery compliance (0.07%/10 mmHg) compared to persistently rural residents. The differences in surrogate markers of CVD were only partially attenuated when adjusted for cardiovascular risk factors. Conclusions: Participants living in urban communities had a more favourable cardiovascular risk factor profile than rural residents. Furthermore, participants continuously living in urban areas had less subclinical markers related to CVD compared with participants living in rural areas. Urban-rural differences in cardiovascular health might provide important opportunities for optimizing prevention by targeting areas of highest need.
  • Finndiane Study Grp; Ahola, Aila J.; Harjutsalo, Valma; Forsblom, Carol; Pouwer, Francois; Groop, Per-Henrik (2021)
    OBJECTIVE To investigate the relationship between depression and diabetic nephropathy progression in type 1 diabetes. RESEARCH DESIGN AND METHODS Data from 3,730 participants without end-stage renal disease (ESRD) at baseline, participating in the Finnish Diabetic Nephropathy Study, were included. Depression was assessed in three ways. Depression diagnoses were obtained from the Finnish Care Register for Health Care. Antidepressant agent purchase data were obtained from the Drug Prescription Register. Symptoms of depression were assessed using the Beck Depression Inventory (BDI). Based on their urinary albumin excretion rate (AER), participants were classified as those with normal AER, microalbuminuria, and macroalbuminuria. Progression from normal AER to microalbuminuria, macroalbuminuria, or ESRD; from microalbuminuria to macroalbuminuria or ESRD; or from macroalbuminuria to ESRD, during the follow-up period, was investigated. RESULTS Over a mean follow-up period of 9.6 years, renal status deteriorated in 18.4% of the participants. Diagnosed depression and antidepressant purchases before baseline were associated with 53% and 32% increased risk of diabetic nephropathy progression, respectively. Diagnosed depression assessed during follow-up remained associated with increased risk of disease progression (32%). BDI-derived symptoms of depression showed no association with the progression, but the total number of antidepressant purchases modestly reduced the risk (hazard ratio 0.989 [95% CI 0.982-0.997]), P = 0.008). With the sample divided based on median age, the observations followed those seen in the whole group. However, symptoms of depression additionally predicted progression in those age
  • Viinikainen, Jutta; Bryson, Alex; Böckerman, Petri; Elovainio, Marko; Hutri-Kahonen, Nina; Juonala, Markus; Lehtimaki, Terho; Pahkala, Katja; Rovio, Suvi; Pulkki-Råback, Laura; Raitakari, Olli; Pehkonen, Jaakko (2020)
    A burgeoning body of literature suggests that poor childhood health leads to adverse health outcomes. lower educational attainment and weaker labour market outcomes in adulthood. We focus on an important but under-researched topic, which is the role played by infection-related hospitalization (IRH) in childhood and its links to labour market outcomes later in life. The participants aged 24-30 years in 2001 N =1706 were drawn from the Young Finns Study, which includes comprehensive registry data on IRHs in childhood at ages 0-18 years. These data are linked to longitudinal registry information on labour market outcomes (2001-2012) and parental background (1980). The estimations were performed using ordinary least squares (OLS). The results showed that having an additional IRH is associated with lower log earnings (b = 95% confidence interval (CI): -0.193; -0.026). fewer years of being employed (b = -0.018. 95% CI: -0.031; -0.005). a higher probability of receiving any social income transfers (b = 0.012, 95 % CI: -0.002; 0.026) and larger social income transfers, conditional on receiving any (b = 0.085,95 % CI: 0.025; 0.145). IRHs are negatively linked to human capital accumulation. which explains a considerable part of the observed associations between IRHs and labour market outcomes. We did not find support for the hypothesis that adult health mediates the link. (C) 2020 The Authors. Published by Elsevier B.V.
  • Yang, Xiaolin; Kaseva, Kaisa; Keltikangas-Jarvinen, Liisa; Pulkki-Raback, Laura; Hirvensalo, Mirja; Jokela, Markus; Hintsanen, Mirka; Hintsa, Taina; Kankaanpää, Anna; Telama, Risto; Hutri-Kahonen, Nina; Viikari, Jorma S. A.; Raitakari, Olli T.; Tammelin, Tuija (2017)
    We examined associations between childhood temperamental activity, physical activity (PA), and television (TV) viewing over a 30-year period. The participants (1220 boys and 1237 girls) were aged 3, 6, 9, and 12 years in 1980 and were followed until 2011. Temperamental activity was evaluated by participants' mothers at baseline. The PA was assessed based on maternal ratings of the child from ages 3 to 6 and via self-report age from the age of 9 across all measurements. TV viewing was assessed using self-reports taken from 2001 to 2011. The associations between temperamental activity and the level and change of PA and TV viewing were determined using linear growth modeling stratified by gender and age group. High temperamental activity assessed from ages 9 to 12 was associated with high levels of childhood PA in both genders, but with a steeper decline in PA levels during the first 9 years of follow-up in boys. High temperamental activity assessed from ages 3 to 6 was associated with the decline of PA from childhood to youth in girls. High childhood temperamental activity was associated with decreased levels of PA in adulthood in men, but not in women. The associations between childhood temperamental activity and TV viewing during adulthood seemed to be positive but not consistently significant in all age and gender groups. High temperamental activity may contribute to the development of a physically inactive lifestyle. More evidence is needed with regard to gender differences among participants in similar study settings.
  • Saarinen, Aino I. L.; Keltikangas-Järvinen, Liisa; Hintsa, Taina; Pulkki-Råback, Laura; Ravaja, Niklas; Lehtimäki, Terho; Raitakari, Olli; Hintsanen, Mirka (2020)
    Background This study investigated (i) whether compassion is associated with blood pressure or hypertension in adulthood and (ii) whether familial risk for hypertension modifies these associations. Method The participants (N = 1112-1293) came from the prospective Young Finns Study. Parental hypertension was assessed in 1983-2007; participants' blood pressure in 2001, 2007, and 2011; hypertension in 2007 and 2011 (participants were aged 30-49 years in 2007-2011); and compassion in 2001. Results High compassion predicted lower levels of diastolic and systolic blood pressure in adulthood. Additionally, high compassion was related to lower risk for hypertension in adulthood among individuals with no familial risk for hypertension (independently of age, sex, participants' and their parents' socioeconomic factors, and participants' health behaviors). Compassion was not related to hypertension in adulthood among individuals with familial risk for hypertension. Conclusion High compassion predicts lower diastolic and systolic blood pressure in adulthood. Moreover, high compassion may protect against hypertension among individuals without familial risk for hypertension. As our sample consisted of comparatively young participants, our findings provide novel implications for especially early-onset hypertension.
  • Wang, Qin; Wurtz, Peter; Auro, Kirsi; Morin-Papunen, Laure; Kangas, Antti J.; Soininen, Pasi; Tiainen, Mika; Tynkkynen, Tuulia; Joensuu, Anni; Havulinna, Aki S.; Aalto, Kristiina; Salmi, Marko; Blankenberg, Stefan; Zeller, Tanja; Viikari, Jorma; Kahonen, Mika; Lehtimaki, Terho; Salomaa, Veikko; Jalkanen, Sirpa; Jarvelin, Marjo-Riitta; Perola, Markus; Raitakari, Olli T.; Lawlor, Debbie A.; Kettunen, Johannes; Ala-Korpela, Mika (2016)
    Background: Hormonal contraception is commonly used worldwide, but its systemic effects across lipoprotein subclasses, fatty acids, circulating metabolites and cytokines remain poorly understood. Methods: A comprehensive molecular profile (75 metabolic measures and 37 cytokines) was measured for up to 5841 women (age range 24-49 years) from three population-based cohorts. Women using combined oral contraceptive pills (COCPs) or progestin-only contraceptives (POCs) were compared with those who did not use hormonal contraception. Metabolomics profiles were reassessed for 869 women after 6 years to uncover the metabolic effects of starting, stopping and persistently using hormonal contraception. Results: The comprehensive molecular profiling allowed multiple new findings on the metabolic associations with the use of COCPs. They were positively associated with lipoprotein subclasses, including all high-density lipoprotein (HDL) subclasses. The associations with fatty acids and amino acids were strong and variable in direction. COCP use was negatively associated with albumin and positively associated with creatinine and inflammatory markers, including glycoprotein acetyls and several growth factors and interleukins. Our findings also confirmed previous results e.g. for increased circulating triglycerides and HDL cholesterol. Starting COCPs caused similar metabolic changes to those observed cross-sectionally: the changes were maintained in consistent users and normalized in those who stopped using. In contrast, POCs were only weakly associated with metabolic and inflammatory markers. Results were consistent across all cohorts and for different COCP preparations and different types of POC delivery. Conclusions: Use of COCPs causes widespread metabolic and inflammatory effects. However, persistent use does not appear to accumulate the effects over time and the metabolic perturbations are reversed upon discontinuation. POCs have little effect on systemic metabolism and inflammation.
  • Miettinen, Helena E.; Rönö, Kristiina; Koivusalo, Saila; Stach-Lempinen, Beata; Pöyhönen-Alho, Maritta; Eriksson, Johan G.; Hiltunen, Timo P.; Gylling, Helena (2014)
  • Mishra, Pashupati P.; Hänninen, Ismo; Raitoharju, Emma; Marttila, Saara; Mishra, Binisha H.; Mononen, Nina; Kähönen, Mika; Hurme, Mikko; Raitakari, Olli; Törönen, Petri; Holm, Liisa; Lehtimaki, Terho (2020)
    Smoking as a major risk factor for morbidity affects numerous regulatory systems of the human body including DNA methylation. Most of the previous studies with genome-wide methylation data are based on conventional association analysis and earliest threshold-based gene set analysis that lacks sensitivity to be able to reveal all the relevant effects of smoking. The aim of the present study was to investigate the impact of active smoking on DNA methylation at three biological levels: 5'-C-phosphate-G-3' (CpG) sites, genes and functionally related genes (gene sets). Gene set analysis was done with mGSZ, a modern threshold-free method previously developed by us that utilizes all the genes in the experiment and their differential methylation scores. Application of such method in DNA methylation study is novel. Epigenome-wide methylation levels were profiled from Young Finns Study (YFS) participants' whole blood from 2011 follow-up using Illumina Infinium Hu-manMethylation450 BeadChips. We identified three novel smoking related CpG sites and replicated 57 of the previously identified ones. We found that smoking is associated with hypomethylation in shore (genomic regions 0-2 kilobases from CpG island). We identified smoking related methylation changes in 13 gene sets with false discovery rate (FDR)
  • FinnGen Project; Locke, Adam E.; Havulinna, Aki S.; Pirinen, Matti; Eriksson, Johan G.; Ala-Korpela, Mika; Järvelin, Marjo-Riitta; Männikkö, Minna; Laivuori, Hannele; Palotie, Aarno; Salomaa, Veikko; Laakso, Markku; Ripatti, Samuli (2019)
    Exome-sequencing studies have generally been underpowered to identify deleterious alleles with a large effect on complex traits as such alleles are mostly rare. Because the population of northern and eastern Finland has expanded considerably and in isolation following a series of bottlenecks, individuals of these populations have numerous deleterious alleles at a relatively high frequency. Here, using exome sequencing of nearly 20,000 individuals from these regions, we investigate the role of rare coding variants in clinically relevant quantitative cardiometabolic traits. Exome-wide association studies for 64 quantitative traits identified 26 newly associated deleterious alleles. Of these 26 alleles, 19 are either unique to or more than 20 times more frequent in Finnish individuals than in other Europeans and show geographical clustering comparable to Mendelian disease mutations that are characteristic of the Finnish population. We estimate that sequencing studies of populations without this unique history would require hundreds of thousands to millions of participants to achieve comparable association power.
  • Marques, Francine Z.; Prestes, Priscilla R.; Byars, Sean G.; Ritchie, Scott C.; Wurtz, Peter; Patel, Sheila K.; Booth, Scott A.; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P.; Curl, Claire L.; Bell, James R.; Wai, Bryan; Srivastava, Piyush M.; Kangas, Antti J.; Soininen, Pasi; Ruohonen, Saku; Kahonen, Mika; Lehtimaki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E.; Lewandowski, Paul A.; Delbridge, Lea M.; Burrell, Louise M.; Inouye, Michael; Harrap, Stephen B.; Charchar, Fadi J. (2017)
    Background-Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. Methods and Results-We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2-knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis-eQTL for LCN2 expression. Conclusions-Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure.
  • Halonen, Jaana I.; Shiri, Rahman; Mänty, Minna; Sumanen, Hilla; Solovieva, Svetlana; Viikari-Juntura, Eira; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Lallukka, Tea (2019)
    Objectives To examine whether exposure to heavy physical work from early to later adulthood is associated with primary healthcare visits due to cause-specific musculoskeletal diseases in midlife. Design Prospective cohort study. Setting Nationally representative Young Finns Study cohort, Finland. Participants 1056 participants of the Young Finns Study cohort. Exposure measure Physical work exposure was surveyed in early (18-24years old, 1986 or 1989) and later adulthood (2007 and 2011), and it was categorised as: 'no exposure', 'early exposure only', 'later exposure only' and 'early and later exposure'. Primary and secondary outcome measures Visits due to any musculoskeletal disease and separately due to spine disorders, and upper extremity disorders were followed up from national primary healthcare register from the date of the third survey in 2011 until 2014. Results Prevalence of any musculoskeletal disease during the follow-up was 20%, that for spine disorders 10% and that for upper extremity disorders 5%. Those with physically heavy work in early adulthood only had an increased risk of any musculoskeletal disease (risk ratio (RR) 1.55, 95% CI 1.05 to 2.28) after adjustment for age, sex, smoking, body mass index, physical activity and parental occupational class. Later exposure only was associated with visits due to any musculoskeletal disease (RR 1.46, 95%CI 1.01 to 2.12) and spine disorders (RR 2.40, 95%CI 1.41 to 4.06). Early and later exposure was associated with all three outcomes: RR 1.99 (95% CI 1.44 to 2.77) for any musculoskeletal disease, RR 2.43 (95% CI 1.42 to 4.14) for spine disorders and RR 3.97 (95% CI 1.86 to 8.46) for upper extremity disorders. Conclusions To reduce burden of musculoskeletal diseases, preventive actions to reduce exposure to or mitigate the consequences of physically heavy work throughout the work career are needed.
  • Cuthbertson, Daniel J.; Koskinen, Juha; Brown, Emily; Magnussen, Costan G.; Hutri-Kahonen, Nina; Sabin, Matthew; Tossavainen, Paivi; Jokinen, Eero; Laitinen, Tomi; Viikari, Jorma; Raitakari, Olli T.; Juonala, Markus (2021)
    Aims To investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up. Methods At baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (= 25-= 30 kg/m(2)) and FLI (as high FLI >= 60 or low FLI
  • Seppa, Satu; Tenhola, Sirpa; Voutilainen, Raimo (2019)
    Context: Among cytokines, fibroblast growth factor 21 (FGF21), adiponectin (Adn), and irisin have been considered potential biomarkers for insulin sensitivity (IS). Objective: We evaluated whether serum FGF21, Adn, and irisin associate with markers of IS and serum lipids in 12-year-old children. Design, Participants, and Main Outcome Measures: This cohort study included 192 12-year-old children (109 girls). Seventy-eight of them had been born appropriate for gestational age (AGA), 70 small for gestational age (SGA), and 44 from preeclamptic pregnancies (PREs) as AGA. Fasting serum FGF21, Adn, irisin, lipids, inflammatory markers, and IS markers were measured. Quantitative insulin sensitivity check index (QUICKI) was calculated. Results: The means of serum FGF21, high molecular weight (HMW) Adn, and irisin did not differ between the sexes or between the SGA, AGA, and PRE children. In the whole study population, FGF21 associated positively with irisin and uric acid and negatively with leptin and high-density lipoprotein cholesterol (HDL-C). HMW Adn associated positively with total Adn, HDL-C, leptin, and SHBG. Apart from FGF21, irisin associated positively with insulin, high-sensitivity C-reactive protein, y-glutamyltransferase, and triglycerides, and negatively with QUICKI, SHBG, and IGF binding protein-1. In multivariate regression analyses, irisin predicted lower IS and HMW Adn predicted higher HDL-C body mass index-independently, whereas FGF21 had no independent contribution to IS or lipid variables. Conclusion: In 12-year-old children, serum irisin was associated with markers reflecting reduced IS. HMW Adn predicted HDL-C, whereas FGF21 did not contribute to IS or lipid parameters in multivariate regression analyses. Copyright (C) 2019 Endocrine Society
  • Bertone-Johnson, Elizabeth R.; Virtanen, Jyrki K.; Nurmi, Tarja; Niskanen, Leo; Mursu, Jaakko; Voutilainen, Sari; Ronkainen, Kimmo; Kauhanen, Jussi; Tuomainen, Tomi-Pekka (2018)
    Recent studies of perimenopausal women suggest that follicle-stimulating hormone (FSH) levels may be associated with atherosclerosis, independent of estradiol. Whether FSH is related to atherosclerosis in older postmenopausal women, who have completed the menopausal transition, remains unknown. We assessed the relationship of serum FSH and estradiol levels with carotid artery intima-media thickness (IMT) among 587 postmenopausal participants in the Kuopio Ischemic Heart Disease Risk Factor Study (Kuopio, Finland). Participants were aged 53-73 years and not using hormone therapy at baseline (1998-2001). Mean IMT was measured via high-resolution ultrasonography. We observed a significant inverse association between FSH levels and IMT. Mean IMTs among women in quartiles 1-4 of FSH were 0.94 mm, 0.91 mm, 0.87 mm, and 0.85 mm, respectively (P-trend <0.001). After adjustment for age, estradiol, testosterone, body mass index (weight (kg)/height (m)(2)), lipids, and other factors, FSH levels remained significantly associated with IMT (regression coefficients for quartiles 2-4 vs. quartile 1 were -0.038, -0.045, and -0.062, respectively; P-trend = 0.01). Findings were strongest in women aged 64-73 years (P-trend = 0.006) and did not vary by body mass index. In contrast, estradiol levels were not related to IMT. In summary, high postmenopausal FSH levels were associated with a lower atherosclerotic burden, independent of estradiol, adiposity, and other factors. Our findings warrant replication and the further exploration of potential underlying mechanisms.
  • Dobewall, Henrik; Savelieva, Kateryna; Seppälä, Ilkka; Knafo-Noam, Ariel; Hakulinen, Christian; Elovainio, Marko; Keltikangas-Jarvinen, Liisa; Pulkki-Råback, Laura; Raitakari, Olli T.; Lehtimäki, Terho; Hintsanen, Mirka (2019)
    Background Genomic analysis of the child might offer new potential to illuminate human parenting. We examined whether offspring (G2) genome-wide genotype variation (SNPs) is associated with their mother's (G1) emotional warmth and intolerance, indicating a gene-environment correlation. If this association is stronger than between G2 ' s genes and their emotional warmth and intolerance toward their own children, then this would indicate the presence of an evocative gene-environment correlation. To further understand how G1 mother's parenting has been evoked by genetically influenced characteristics of the child (G2), we examined whether child (G2) temperament partially accounted for the association between offspring genes and parental responses. Methods Participants were from the Young Finns Study. G1 mothers (N = 2,349; mean age 39 years) self-reported the emotional warmth and intolerance toward G2 in 1980 when the participants were from 3 to 18 years old. G2 participants answered the same parenting scales in 2007/2012 (N = 1,378; mean age = 38 years in 2007; 59% female) when their children were on average 11 years old. Offspring temperament traits were self-reported in 1992 (G2 age range 15-30 years). Estimation of the phenotypic variance explained by the SNPs of G2 was done by genome-wide complex trait analysis with restricted maximum likelihood (GCTA-GREML). Results Results showed that the SNPs of a child (G2) explained 22.6% of the phenotypic variance of maternal intolerance (G1; p-value = .039). G2 temperament trait negative emotionality explained only 2.4% points of this association. G2 genes did not explain G1 emotional warmth or G2 ' s own emotional warmth and intolerance. However, further analyses of a combined measure of both G1 parenting scales found genetic effects. Parent or child gender did not moderate the observed associations. Conclusions Presented genome-wide evidence is pointing to the important role a child plays in affecting and shaping his/her family environment, though the underlying mechanisms remain unclear.
  • Huang, Yisong; Ollikainen, Miina; Sipilä, Pyry; Mustelin, Linda; Wang, Xin; Su, Shaoyong; Huan, Tianxiao; Levy, Daniel; Wilson, James; Snieder, Harold; Kaprio, Jaakko; Wang, Xiaoling (2018)
    Recently, 2 transcriptome-wide studies identified 40 genes that were differentially expressed in relation to blood pressure. However, to what extent these BP-related gene expression signatures and their associations with BP are driven by genetic or environmental factors has not been investigated. In this study of 391 twins (193 twin pairs and 5 singletons; age 55-69 years; 40% male; 57% monozygous) recruited from the Finnish Twin Cohort, transcriptome-wide data on peripheral leukocytes were obtained using the Illumina HT12 V4 array. Our transcriptome-wide analysis identified 1 gene (MOK [MAPK/MAK/MRK overlapping kinase], P=7.16x10(-8)) with its expression levels associated with systolic BP at the cutoff of false-discovery rate
  • Jia, Qiong; Han, Yi; Huang, Pin; Woodward, Nicholas C.; Gukasyan, Janet; Kettunen, Johannes; Ala-Korpela, Mika; Anufrieva, Olga; Wang, Qin; Perola, Markus; Raitakari, Olli; Lehtimaki, Terho; Viikari, Jorma; Jarvelin, Marjo-Riitta; Boehnke, Michael; Laakso, Markku; Mohlke, Karen L.; Fiehn, Oliver; Wang, Zeneng; Tang, W. H. Wilson; Hazen, Stanley L.; Hartiala, Jaana A.; Allayee, Hooman (2019)
    Background-Recent studies have revealed sexually dimorphic associations between the carbamoyl-phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease (CAD) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl-phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results-We sought to identify additional genetic determinants of circulating glycine levels by carrying out a metaanalysis of genome-wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine-associated variants were associated with CAD and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism (ACADM, PHGDH, COX1 8-ADAMTS3, PSPH, TRIB 1 , PTPRD, and ABO). Glycine-raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of CAD. However, these effects could not be attributed directly to glycine because of associations with other CAD-related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of CAD or blood pressure, lipid levels, and obesity-related traits. Conclusions-These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of CAD in humans.
  • Nissinen, Markku J.; Pitkänen, Niina; Simonen, Piia; Gylling, Helena; Viikari, Jorma; Raitakari, Olli; Lehtimäki, Terho; Juonala, Markus; Pakarinen, Mikko P. (2018)
    Background & aims: Gallstone disease is related to hypersecretion of cholesterol in bile, and low serum phytosterol levels. We examined how genetic polymorphisms of sterol transporters affect childhood cholesterol metabolism trait predicting adult gallstone disease. Patients and methods: In retrospective controlled study, we determined D19H polymorphism of ABCG8 gene, genetic variation at Niemann-Pick C1-like 1 (NPC1L1) gene locus (rs41279633, rs17655652, rs2072183, rs217434 and rs2073548), and serum cholesterol, noncholesterol sterols and lipids in children affected by gallstones decades later (n = 66) and controls (n = 126). Results: In childhood, phytosterols were lower (9.7%-23.4%) in carriers of risk allele 19H compared to 19D homozygotes. Lowest campesterol/cholesterol tertile consisted of 1.9-times more future gallstone subjects, and 3.7-times more 19H carriers than highest one. Campesterol/cholesterol-ratio was highest in 19D homozygote controls, but similar to 11% lower in gallstone 19D homozygotes and similar to 25% lower among gallstone and control carriers of 19H. Gallstone subjects with alleles CC of rs41279633 and TT of rs217434 of NPC1L1 had similar to 18% lower campesterol/cholesterol-ratio compared to mutation carriers. Conclusions: Risk trait of cholesterol metabolism (low phytosterols) in childhood favouring cholesterol gallstone disease later in adulthood is influenced by risk variant 19H of ABCG8 and obviously also other factors. NPC1L1 variants have minor influence on noncholesterol sterols. (c) 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.