CACNB2 Is a Novel Susceptibility Gene for Diabetic Retinopathy in Type 1 Diabetes

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dc.contributor University of Helsinki, Department of Medicine en
dc.contributor University of Helsinki, HUS Abdominal Center en
dc.contributor University of Helsinki, HUS Abdominal Center en
dc.contributor University of Helsinki, HUS Abdominal Center en
dc.contributor University of Helsinki, Research Programs Unit en
dc.contributor University of Helsinki, HUS Head and Neck Center en
dc.contributor University of Helsinki, HUS Abdominal Center en
dc.contributor University of Helsinki, HUS Abdominal Center en
dc.contributor.author FinnDiane Study
dc.contributor.author Vuori, Nadja
dc.contributor.author Sandholm, Niina
dc.contributor.author Kumar, Anmol
dc.contributor.author Hietala, Kustaa
dc.contributor.author Syreeni, Anna
dc.contributor.author Forsblom, Carol
dc.contributor.author Juuti-Uusitalo, Kati
dc.contributor.author Skottman, Heli
dc.contributor.author Imamura, Minako
dc.contributor.author Maeda, Shiro
dc.contributor.author Summanen, Paula A.
dc.contributor.author Lehto, Markku
dc.contributor.author Groop, Per-Henrik
dc.date.accessioned 2019-11-08T07:33:02Z
dc.date.available 2019-11-08T07:33:02Z
dc.date.issued 2019-11
dc.identifier.citation FinnDiane Study , Vuori , N , Sandholm , N , Kumar , A , Hietala , K , Syreeni , A , Forsblom , C , Juuti-Uusitalo , K , Skottman , H , Imamura , M , Maeda , S , Summanen , P A , Lehto , M & Groop , P-H 2019 , ' CACNB2 Is a Novel Susceptibility Gene for Diabetic Retinopathy in Type 1 Diabetes ' , Diabetes , vol. 68 , no. 11 , pp. 2165-2174 . https://doi.org/10.2337/db19-0130 en
dc.identifier.issn 0012-1797
dc.identifier.other PURE: 127985689
dc.identifier.other PURE UUID: 45cc4473-e70a-4f5e-870c-a5f42c080a72
dc.identifier.other WOS: 000491455200011
dc.identifier.other ORCID: /0000-0003-4322-6942/work/64324500
dc.identifier.other ORCID: /0000-0003-0549-9819/work/64325592
dc.identifier.uri http://hdl.handle.net/10138/306827
dc.description.abstract Diabetic retinopathy is a common diabetes complication that threatens the eyesight and may eventually lead to acquired visual impairment or blindness. While a substantial heritability has been reported for proliferative diabetic retinopathy (PDR), only a few genetic risk factors have been identified. Using genome-wide sib pair linkage analysis including 361 individuals with type 1 diabetes, we found suggestive evidence of linkage with PDR at chromosome 10p12 overlapping the CACNB2 gene (logarithm of odds = 2.73). Evidence of association between variants in CACNB2 and PDR was also found in association analysis of 4,005 individuals with type 1 diabetes with an odds ratio of 0.83 and P value of 8.6 x 10(-4) for rs11014284. Sequencing of CACNB2 revealed two coding variants, R476C/rs202152674 and S502L/rs137886839. CACNB2 is abundantly expressed in retinal cells and encodes the beta 2 subunit of the L-type calcium channel. Blocking vascular endothelial growth factor (VEGF) by intravitreous anti-VEGF injections is a promising clinical therapy to treat PDR. Our data show that L-type calcium channels regulate VEGF expression and secretion from retinal pigment epithelial cells (ARPE19) and support the role of CACNB2 via regulation of VEGF in the pathogenesis of PDR. However, further genetic and functional studies are necessary to consolidate the findings. en
dc.format.extent 10
dc.language.iso eng
dc.relation.ispartof Diabetes
dc.rights en
dc.subject ENDOTHELIAL GROWTH-FACTOR en
dc.subject GENOME-WIDE ASSOCIATION en
dc.subject PROLIFERATIVE RETINOPATHY en
dc.subject CUMULATIVE INCIDENCE en
dc.subject BETA(2) SUBUNIT en
dc.subject RISK en
dc.subject PROGRESSION en
dc.subject CHANNELS en
dc.subject LINKAGE en
dc.subject CELLS en
dc.subject 3121 Internal medicine en
dc.title CACNB2 Is a Novel Susceptibility Gene for Diabetic Retinopathy in Type 1 Diabetes en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.2337/db19-0130
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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