Abstract
Objective There is increasing evidence of a strong genetic component in type 2 diabetes (T2DM) that may contribute to diabetes complications. Given the high prevalence of diabetes with its associated complications in the Middle East, we sought to determine if the genotype within a Middle East population may be contributory. Therefore, three genotype-based Qatari ancestral groups, Q1 Arab Bedouin, Q2 Asian/Persian, and Q3 sub-Saharan African, with a fourth admixed group were correlated with T2DM prevalence and its complications to determine if they differed between the 4 Qatari ancestries, particularly for the SLMAP allele-associated diabetic retinopathy. Methods In this cross-sectional study, 398 Qatari subjects, 220 with and 178 without T2DM, were genotyped by Affymetrix 500k SNP arrays. Ancestry was correlated with diabetes complications. Results 398 subjects were included, the mean age was 49.8 years, and 56.8% were male. The genotype-based ancestry and T2DM prevalence were as follows: 164 (41.2%) with ancestry Q1, 60.4% with T2DM; 149 (37.4%) with ancestry Q2, 49.7% with T2DM; 31 (7.8%) with ancestry Q3, 61.3% with T2DM; and 54 (13.6%) with “admixed” ancestry, 51.9% with T2DM. For patients with diabetes, hypertension (p < 0.035) and retinopathy (p < 0.016) were greater in the Q3 ancestry. Conclusion These data suggest that the genotype may contribute to complication risk, as exemplified by the increase in hypertension and retinopathy in the Q3 ancestry, though the SLMAP allele was not implicated; however, diabetes prevalence did not differ between the four Qatari ancestries.
Highlights
Type 2 diabetes (T2DM) is a complex disease with a heterogeneous genetic component that has not been fully determined, hindering attempts at personalized medicine [1]
Stratification of diabetes into multiple subtypes has shown that diabetes complications differed across them [13] and that there was a clustering of genetic associations
In accordance with these observations, it can be seen that both retinopathy and hypertension appeared to be linked to the Q3 sub-Saharan ancestry when compared with the Q1 Arab/Bedouin, Q2 Persian/South Asian, and admixed ancestries
Summary
Type 2 diabetes (T2DM) is a complex disease with a heterogeneous genetic component that has not been fully determined, hindering attempts at personalized medicine [1]. Diabetes is prevalent in the Middle East with approximately 20% of the population having T2DM, a figure 2-3 times higher than the world average [2]. Next-generation exome sequencing has identified three major genotype-based ancestry groups within the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, and Q3 African) and has identified variants within genes that have effects on clinically significant Mendelian diseases [4,5,6]. Several of these Mendelian variants were segregated only in one Qatari ancestry group [5]. Others have looked at the SLMAP gene in the Qatari population and found that the SLMAP C>T polymorphism is associated, as an independent risk factor for retinopathy [8]
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