Association of Differing Qatari Genotypes with Vitamin D Metabolites

Abstract

This work aimed to determine the possible association between Qatari genotypes and vitamin-D deficiency and diabetes complications. Through next-generation exome sequencing three major genetic Qatari genotypes were determined, Q1 - Bedouin, Q2 - Persian-South Asian and Q3 - African. The hypothesis was that Qatari genotypes would affect vitamin D and metabolite levels independent of cultural factors, perhaps exacerbated by diabetes.Materials and Methods. Affymetrix 500k SNP arrays determined 398 Qataris genotype (mean age 49.8 years, 56.8% male; type 2 diabetes (T2DM) 220; control 178). LC-MS/MS analysis measured 1,25-dihydroxyvitamin-D (1,25(OH)2D), 25-hydroxyvitamin-D2 (25(OH)D2), 25-hydroxyvitamin-D3 (25(OH)D3), 24,25-dihydroxyvitamin-D (24,25(OH)2D) and 25-hydroxy-3epi-Vitamin-D (3epi25(OH)D). The same study population was used to investigate the association of diabetes and its complications with various genotypes.Results. There was no difference in 25(OH)D levels between genotype groups; however, 1,25(OH)2D was higher for Q2 and 24,25(OH)2D was higher in Q1 compared to the ‘admixed’ group. Additionally, the genotype-based ancestry and type 2 diabetes (T2DM) prevalence: 164 (41.2%) with Q1, 60.4% with T2DM; 149 (37.4%) with Q2, 49.7% with T2DM; 31 (7.8%) with Q3, 61.3% with T2DM; and 54 (13.6%) with “admixed”, 51.9% with T2DM. In patients with diabetes, hypertension (p<0.035) and retinopathy (p<0.016) were greater in Q3.Conclusion. Overall, the study population was vitamin-D deficient, total 25(OH)D was higher in patients with concomitant T2DM, 1,25(OH)2D, 24,25(OH)2D and 3epi25(OH)D were lower in diabetes. Vitamin D levels were not associated with a specific genotype. Q3 was found to have a higher frequency of diabetic retinopathy and hypertension

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