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Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population.

ABSTRACT: Overexpression of SLMAP gene has been associated with diabetes and endothelial dysfunction of macro- and micro-blood vessels. In this study our primary objective is to explore the role of SLMAP gene polymorphisms in the susceptibility of type 2 diabetes (T2DM) with or without diabetic retinopathy (DR) in the Qatari population.A total of 342 Qatari subjects (non-diabetic controls and T2DM patients with or without DR) were genotyped for SLMAP gene polymorphisms (rs17058639 C?>?T; rs1043045 C?>?T and rs1057719 A?>?G) using Taqman SNP genotyping assay.SLMAP rs17058639 C?>?T polymorphism was associated with the presence of DR among Qataris with T2DM. One-way ANOVA and multiple logistic regression analysis showed SLMAP SNP rs17058639 C?>?T as an independent risk factor for DR development. SLMAP rs17058639 C?>?T polymorphism also had a predictive role for the severity of DR. Haplotype Crs17058639Trs1043045Ars1057719 was associated with the increased risk for DR among Qataris with T2DM.The data suggests the potential role of SLMAP SNPs as a risk factor for the susceptibility of DR among T2DM patients in the Qatari population.

SUBMITTER: Upadhyay R

PROVIDER: S-EPMC4335364 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population.

Upadhyay Rohit R Robay Amal A Fakhro Khalid K Abi Khalil Charbel C Zirie Mahmoud M Jayyousi Amin A El-Shafei Maha M Kiss Szilard S D'Amico Donald J DJ Salit Jacqueline J Staudt Michelle R MR O'Beirne Sarah L SL Chen Xiaoliang X Tuana Balwant B Crystal Ronald G RG Ding Hong H

Journal of translational medicine 20150215

<h4>Background</h4>Overexpression of SLMAP gene has been associated with diabetes and endothelial dysfunction of macro- and micro-blood vessels. In this study our primary objective is to explore the role of SLMAP gene polymorphisms in the susceptibility of type 2 diabetes (T2DM) with or without diabetic retinopathy (DR) in the Qatari population.<h4>Methods</h4>A total of 342 Qatari subjects (non-diabetic controls and T2DM patients with or without DR) were genotyped for SLMAP gene polymorphisms ( ...[more]

PMID: 25880194

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Project description:Patients with long-duration diabetes develop cardiovascular complications resulting in highly increased mortality and complications which affect the kidneys, eyes and peripheral nerves associated with high morbidity. Among the diabetic complications, damage in the eye, diabetic retinopathy, is the most common microvascular complication of diabetes. Diabetic retinopathy is a leading cause of vision-loss globally. It is characterized by a number of different patho-mechanisms including changes in vascular permeability, capillary degeneration, and finally at a late stage overshooting formation of new blood vessels. This expression analysis focused on the use of different experimental models for Diabetes Mellitus and its complications (for a review see 1: Al-Awar et al: Experimental Diabetes Mellitus in Different Animal Models. J Diabetes Res. 2016; doi: 10.1155/2016/9051426). By that, we wanted to uncover the relative contributions of systemic hyperinsulinaemia and/or hyperglycemia to molecular regulations. The following models have been used: As insulinopenic, hyperglycemic model reflecting Type 1 diabetes, male STZ-Wistar rats (60mg/kg BW; i.p.) were used. Wistar rats without STZ injection served as non-diabetic controls. Male obese ZDF rats (Fa/Fa) were used as type-2 diabetes model characterized by persisting hyperglycemia and transient hyperinsulinemia. Male lean ZDF rats (Fa/-) served as non-diabetic controls. Male obese ZF rats (Fa/Fa) hyperglycemia were used reflecting euglycemia and severe insulin resistance. Male lean ZF rats (Fa/-) served as controls. ZDF and ZF rats were obtained in two genotypes, obese (genotype fa/fa) and lean littermates (genotype Fa/?). All rats were housed in standard cages under a normal light-dark cycle for 16 weeks. All animals had free access to food and water. ZF and Wistar rats received a standard chow (Ssniff R/M) and ZDF rats received Purina 5008 chow. A group size of n=8 were used for all study groups. Wistar rats were rendered type-1 like hyperglycemic and hypoinsulinemic via a single injection of streptocotocin (STZ, 60mg/kg; i.p.) at 7 weeks of age. Obese ZDF rats (fa/fa) develop spontaneously a type-2 diabetes phenotype with persisting hyperglycemia and transient hyperinsulinemia (hyperglycemic, hypoinsulinemic). Obese ZF rats (fa/fa) develop insulin resistance with permanent hyperinsulinemia without concomitant hyperglycemia and no overt diabetes phenotype. Non STZ treated Wistar rats, lean ZDF littermates (Fa/?), and lean ZF littermates (Fa/?) served as controls. All groups were kept for 12 weeks on respective conditions together with appropriate age-matched controls. Unbiased gene expression analysis was performed per group using Affymetrix gene arrays.

Project description:Genome-wide association studies have successfully identified over 70 loci associated with the risk of type 2 diabetes mellitus (T2DM) in multiple populations of European ancestry. However, the risk attributable to an individual variant is modest and does not yet provide convincing evidence for clinical utility. Association between these established genetic variants and T2DM in general populations is hitherto understudied in the isolated populations, such as the Uyghurs, resident in Hetian, far southern Xinjiang Uyghur Autonomous Region, China. In this case-control study, we genotyped 13 single-nucleotide polymorphisms (SNPs) at 10 genes associated with diabetes in 130 cases with T2DM and 135 healthy controls of Uyghur, a Chinese minority ethnic group. Three of the 13 SNPs demonstrated significant association with T2DM in the Uyghur population. There were significant differences between the T2DM patients and controls in the risk allele distributions of rs3792267 (CAPN10) (P = 0.002), rs1501299 (APM1) (P = 0.017), and rs3760776 (FUT6) (P = 0.031). Allelic carriers of rs3792267-A, rs1501299-T, and rs3760776-T had a 2.24-fold [OR (95% CI): 1.35-3.71], 0.59-fold [OR (95% CI): 0.39-0.91], 0.57-fold [OR (95% CI): 0.34-0.95] increased risk for T2DM respectively. We further confirmed that the cumulative risk allelic scores calculated from the 13 susceptibility loci for T2DM differed significantly between the T2DM patients and controls (P = 0.001), and the effect of obesity/overweight on T2DM was only observed in the subjects with a combined risk allelic score under a value of 17. This study observed that the SNPs rs3792267 in CAPN10, rs1501299 in APM1, and rs3760776 in FUT6 might serve as potential susceptible biomarkers for T2DM in Uyghurs. The cumulative risk allelic scores of multiple loci with modest individual effects are also significant risk factors in Uyghurs for T2DM, particularly among non-obese individuals. This is the first investigation having observed/found genetic variations on genetic loci functionally linked with glycosylation associated with the risk of T2DM in a Uyghur population.

Dataset Information

Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population.

Publications

Role of SLMAP genetic variants in susceptibility of diabetes and diabetic retinopathy in Qatari population.

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