Abstract
BackgroundWe evaluated the associations between single nucleotide polymorphisms and different clinical parameters related to type 2 diabetes mellitus (T2DM), obesity risk, and metabolic syndrome (MS) in a Kazakh cohort.MethodsA total of 1336 subjects, including 408 T2DM patients and 928 control subjects, were recruited from an outpatient clinic and genotyped for 32 polymorphisms previously associated with T2DM and obesity-related phenotypes in other ethnic groups. For association studies, the chi-squared test or Fisher’s exact test for binomial variables were used. Logistic regression was conducted to explore associations between the studied SNPs and the risk of developing T2DM, obesity, and MS, after adjustments for age and sex.ResultsAfter excluding four SNPs due to Hardy-Weinberg disequilibrium, significant associations in age-matched cohorts were found betweenT2DM and the following SNPs: rs9939609 (FTO), rs13266634 (SLC30A8), rs7961581 (TSPAN8/LGR5), and rs1799883 (FABP2). In addition, examination of general unmatched T2DM and control cohorts revealed significant associations between T2DM and SNPsrs1799883 (FABP2) and rs9939609 (FTO). Furthermore, polymorphisms in the FTO gene were associated with increased obesity risk, whereas polymorphisms in the FTO and FABP2 genes were also associated with the risk of developing MS in general unmatched cohorts.ConclusionWe confirmed associations between polymorphisms within the SLC30A8, TSPAN8/LGR5, FABP2, and FTO genes and susceptibility to T2DM in a Kazakh cohort, and revealed significant associations with anthropometric and metabolic traits. In particular, FTO and FABP2 gene polymorphisms were significantly associated with susceptibility to MS and obesity in this cohort.
Highlights
We evaluated the associations between single nucleotide polymorphisms and different clinical parameters related to type 2 diabetes mellitus (T2DM), obesity risk, and metabolic syndrome (MS) in a Kazakh cohort
Because the control group consisted of subjects younger than those in T2DM group, to avoid bias, a subset of control subjects was agematched to diabetic subjects (n = 141controls, and n = 223cases) as closely as possible, with a median age of years in control group and years in the T2DM group
In the present study, we addressed whether genetic variants previously reported [8, 12, 23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43] to be associated with susceptibility to T2DM, obesity, and MS in other ethnic groups are associated with obesity-related phenotypes and/or diseases in a Kazakh cohort
Summary
We evaluated the associations between single nucleotide polymorphisms and different clinical parameters related to type 2 diabetes mellitus (T2DM), obesity risk, and metabolic syndrome (MS) in a Kazakh cohort. Type 2 diabetes mellitus (T2DM) is the most widespread endocrine disease and one of the most acute medical and societal problems, as it leads to early disability and increased mortality from different complications [1, 2]. Sikhayeva et al BMC Medical Genetics (2017) 18:76 studies have revealed connections between T2DM and obesity and metabolic syndrome (MS). Genetic variation and environmental factors are thought to contribute to the development of T2DM. The greatest progress in the identification of genetic factors underlying T2DM has been achieved using genome-wide association studies (GWAS) in different populations [6]. Positive associations need to be evaluated in other ethnic populations, due to associated differences in the frequencies of genetic variants, and because of differences in the contribution of environmental factors [6,7,8,9,10]
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