Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

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Hjort , R , Lofvenborg , J E , Ahlqvist , E , Alfredsson , L , Andersson , T , Grill , V , Groop , L , Sorgjerd , E P , Tuomi , T , Åsvold , B O & Carlsson , S 2019 , ' Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes ' , Journal of Clinical Endocrinology and Metabolism , vol. 104 , no. 10 , pp. 4815-4826 . https://doi.org/10.1210/jc.2019-00183

Title: Interaction Between Overweight and Genotypes of HLA, TCF7L2, and FTO in Relation to the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes
Author: Hjort, Rebecka; Lofvenborg, Josefin E.; Ahlqvist, Emma; Alfredsson, Lars; Andersson, Tomas; Grill, Valdemar; Groop, Leif; Sorgjerd, Elin P.; Tuomi, Tiinamaija; Åsvold, Bjorn Olav; Carlsson, Sofia
Contributor: University of Helsinki, Centre of Excellence in Complex Disease Genetics
University of Helsinki, Centre of Excellence in Complex Disease Genetics
Date: 2019-10
Language: eng
Number of pages: 12
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
URI: http://hdl.handle.net/10138/312968
Abstract: Objective: We investigated potential interactions between body mass index (BMI) and genotypes of human leukocyte antigen (HLA), TCF7L2-rs7903146, and FTO-rs9939609 in relation to the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. Methods: We pooled data from two population-based studies: (i) a Swedish study with incident cases of LADA [positive for glutamic acid decarboxylase autoantibodies (GADA); n = 394) and type 2 diabetes (negative for GADA; n = 1290) and matched controls without diabetes (n = 2656) and (ii) a prospective Norwegian study that included incident cases of LADA (n = 131) and type 2 diabetes (n = 1901) and 886,120 person-years of follow-up. Analyses were adjusted for age, sex, physical activity, and smoking. Interaction between overweight (BMI >= 25 kg/m(2)) and HLA/TCF7L2/FTO high-risk genotypes was assessed by attributable proportion due to interaction (AP). Results: The combination of overweight and high-risk genotypes of HLA, TCF7L2, and FTO was associated with pooled relative risk (RRpooled) of 7.59 (95% CI, 5.27 to 10.93), 2.65 (95% CI, 1.97 to 3.56), and 2.21 (95% CI, 1.60 to 3.07), respectively, for LADA, compared with normal-weight individuals with low/intermediate genetic risk. There was a significant interaction between overweight and HLA (AP, 0.29; 95% CI, 0.10 to 0.47), TCF7L2 (AP, 0.31; 95% CI, 0.09 to 0.52), and FTO (AP, 0.38; 95% CI, 0.15 to 0.61). The highest risk of LADA was seen in overweight individuals homozygous for the DR4 genotype [RR, 26.76 (95% CI, 15.42 to 46.43); AP, 0.58 (95% CI, 0.32 to 0.83) (Swedish data)]. Overweight and TCF7L2 also significantly interacted in relation to type 2 diabetes (AP, 0.26; 95% CI, 0.19 to 0.33), but no interaction was observed with high-risk genotypes of HLA or FTO. Conclusions: Overweight interacts with HLA high-risk genotypes but also with genes associated with type 2 diabetes in the promotion of LADA.
Subject: BODY-MASS INDEX
GENE VARIANTS
OBESITY
AUTOANTIBODIES
ASSOCIATION
DQ
HETEROGENEITY
POPULATION
MECHANISMS
CHILDREN
3121 General medicine, internal medicine and other clinical medicine
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