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P-selectin Plasma Levels and Genetic Variant Associated With Diabetic Retinopathy in African Americans.

ABSTRACT: To report the prevalence and risk factors for retinopathy in African Americans with impaired fasting glucose (IFG) and type 2 diabetes in the Jackson Heart Study and to determine if P-selectin plasma levels are independently associated with retinopathy in this population.Prospective, cross-sectional observational study.setting: Community-based epidemiologic study.Total of 629 patients with type 2 diabetes and 266 participants with impaired fasting glucose.Bilateral, 7-field fundus photographs were scored by masked readers for diabetic retinopathy (DR) level. Covariate data including P-selectin plasma levels and genotypes were collected in a standardized fashion.Association between risk factors, including P-selectin plasma levels and genotypes, and retinopathy.The prevalences of any retinopathy among participants with IFG and type 2 diabetes were 9.4% and 32.4%, respectively. Among those with type 2 diabetes, in multivariate models adjusted for age, sex, and other traditional risk factors, higher P-selectin levels were associated with any DR (odds ratio = 1.11, 95% confidence interval = 1.02-1.21, P = .02) and proliferative DR (odds ratio = 1.23, 95% confidence interval = 1.03-1.46, P = .02). To further investigate the relationship between P-selectin and DR, we examined the association between P-selectin genotype and DR. Minor allele homozygotes for the variant rs6128 were less likely to develop DR (P after Bonferroni correction = 0.03).Both serologic and genetic data show an association between P-selectin and DR in the Jackson Heart Study. If confirmed in other studies, this association may provide insight into the pathogenesis of retinopathy.

SUBMITTER: Penman A

PROVIDER: S-EPMC4426234 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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P-selectin Plasma Levels and Genetic Variant Associated With Diabetic Retinopathy in African Americans.

Penman Alan A Hoadley Suzanne S Wilson James G JG Taylor Herman A HA Chen Ching J CJ Sobrin Lucia L

American journal of ophthalmology 20150317 6

<h4>Purpose</h4>To report the prevalence and risk factors for retinopathy in African Americans with impaired fasting glucose (IFG) and type 2 diabetes in the Jackson Heart Study and to determine if P-selectin plasma levels are independently associated with retinopathy in this population.<h4>Design</h4>Prospective, cross-sectional observational study.<h4>Methods</h4>setting: Community-based epidemiologic study.<h4>Study population</h4>Total of 629 patients with type 2 diabetes and 266 participant ...[more]

PMID: 25794792

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Project description:Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10-17, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10-6, β = -0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = -0.09), VEGFA (rs11755845 p = 0.01, β = -0.13), and NFIA (rs334699 p = 1.50×10-3, β = -0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more diverse populations.

Dataset Information

P-selectin Plasma Levels and Genetic Variant Associated With Diabetic Retinopathy in African Americans.

Publications

P-selectin Plasma Levels and Genetic Variant Associated With Diabetic Retinopathy in African Americans.

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