Dataset Information

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

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 × 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 ?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.

SUBMITTER: Vuori N

PROVIDER: S-EPMC6804633 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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<i>CACNB2</i> Is a Novel Susceptibility Gene for Diabetic Retinopathy in Type 1 Diabetes.

Vuori Nadja N Sandholm Niina N Kumar Anmol A Hietala Kustaa K Syreeni Anna A Forsblom Carol C Juuti-Uusitalo Kati K Skottman Heli H Imamura Minako M Maeda Shiro S Summanen Paula A PA Lehto Markku M Groop Per-Henrik PH

Diabetes 20190822 11

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 <i>CACNB2</i> gene (l ...[more]

PMID: 31439644

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Project description:AIM:To investigate the association between a set of six candidate genes and the risk of diabetic retinopathy (DR) in an urban community cohort of Chinese patients with type 2 diabetes mellitus (T2DM). METHODS:A population-based cross-sectional study. The diabetic subjects were recruited from an urban community in Beijing and categorized into groups of proliferative diabetic retinopathy (PDR), non-proliferative diabetic retinopathy (NPDR), or diabetic without any retinopathy (DWR) based on the fundus photography and duration of diabetes. Six candidate genes, including advanced glycation end product specific receptor (AGER), aldose reductase (AKR1B1), inducible nitric oxide synthase (iNOS), pigment epithelium derived factor (PEDF), tumor necrosis factor-alpha (TNF-α), and paraoxonase 1 (PON1), were chosen based on Meta-analysis of genetic association studies for DR and biochemical pathways implicated in DR progression. The allele and genotype distribution of 21 functional single-nucleotide polymorphisms (SNPs) in those 6 candidate genes were investigated using MassARRAY genotyping system. RESULTS:Among 1461 diabetic patients recruited from community, 569 were selected in following genotyping analysis, including 97 patients with PDR, 217 with NPDR, and 255 with DWR. For the promoter variant rs1051993 in AGER gene, the distribution of allele and genotype in PDR group differed from that in DWR group (allele: P=0.011; genotype: P=0.01). Compared with DWR, patients with PDR had lower frequencies of heterozygous genotype GT (9.8% for DWR, 1% for PDR, OR: 0.10, 95%CI: 0.01-0.72) and minor allele T (4.9% for DWR, 0.5% for PDR, OR: 0.10, 95%CI: 0.01-0.75). In multivariate model, the distribution of genotype for rs1051993 in PDR group was significantly different from that in DWR group (GT vs GG: OR: 0.07, 95%CI: 0.01-0.61, P<0.001). No association with DR was observed in other genotyped SNPs. CONCLUSION:The data suggest a significant association of the promoter variant rs1051993 in AGER gene with PDR in Chinese cohort with T2DM.

Dataset Information

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

Publications

<i>CACNB2</i> Is a Novel Susceptibility Gene for Diabetic Retinopathy in Type 1 Diabetes.

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