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

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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

Title: CACNB2 Is a Novel Susceptibility Gene for Diabetic Retinopathy in Type 1 Diabetes
Author: FinnDiane Study; Vuori, Nadja; Sandholm, Niina; Kumar, Anmol; Hietala, Kustaa; Syreeni, Anna; Forsblom, Carol; Juuti-Uusitalo, Kati; Skottman, Heli; Imamura, Minako; Maeda, Shiro; Summanen, Paula A.; Lehto, Markku; Groop, Per-Henrik
Contributor: University of Helsinki, Department of Medicine
University of Helsinki, HUS Abdominal Center
University of Helsinki, HUS Abdominal Center
University of Helsinki, HUS Abdominal Center
University of Helsinki, Research Programs Unit
University of Helsinki, HUS Head and Neck Center
University of Helsinki, HUS Abdominal Center
University of Helsinki, HUS Abdominal Center
Date: 2019-11
Number of pages: 10
Belongs to series: Diabetes
ISSN: 0012-1797
URI: http://hdl.handle.net/10138/306827
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.
Subject: ENDOTHELIAL GROWTH-FACTOR
GENOME-WIDE ASSOCIATION
PROLIFERATIVE RETINOPATHY
CUMULATIVE INCIDENCE
BETA(2) SUBUNIT
RISK
PROGRESSION
CHANNELS
LINKAGE
CELLS
3121 Internal medicine
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