Association between 28 single nucleotide polymorphisms and type 2 diabetes mellitus in the Kazakh population: a case-control study

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-017-0443-2) contains supplementary material, which is available to authorized users.

Associations between the components of metabolic syndrome and the polymorphisms in the peroxisome proliferator-activated receptor gamma (PPAR-γ), the fat mass and obesity-associated (FTO), and the melanocortin-4 receptor (MC4R) genes

“…Over the recent decades, great interest in the impact of the FTO rs9939609 polymorphism on the occurrence of body weight related abnormalities [ 12 , 14 – 17 ], as well as lipid and carbohydrate metabolism [ 29 ] has been observed. The Kazakh cohort study demonstrated that polymorphisms in the FTO gene strongly predisposed to MetS.…”

“…The Kazakh cohort study demonstrated that polymorphisms in the FTO gene strongly predisposed to MetS. The carriers of the A allele were more likely to develop MetS-related abnormalities than their counterparts with the T allele [ 29 ]. These findings correspond with the results obtained by Freathy et al [ 30 ].…”

“…Sikhayeva et al reported on the relationship between type 2 diabetes and the FTO rs9939609 polymorphism in their cohort study of the Kazakh population. The authors observed that in the group with type 2 diabetes, the A allele was substantially more common than the T allele [ 29 ]. Muller et al, on the other hand, did not find any association between this gene and the parameters of the carbohydrate and lipid metabolism [ 31 ].…”

“…Sikhayeva et al found no confirmation for the relationship between the FTO polymorphism and the TG level, but reported on its association with the LDL level. The A/A genotype entailed significantly higher LDL levels compared to the A/T and T/T genotypes [ 29 ]. In our study, the A/T genotype in the overdominant model helped maintain an adequate HDL level, while the T/T-A/A genotypes were more often accompanied by HDL levels <50 mg/dl, but this relationship was not statistically significant.…”

Exposure of Fat Mass Obesity Gene Polymorphism in Diabetes Mellitus Type-II Females of Hyderabad, Sindh

“…The prevalence of T2DM in Sindh province of Pakistan is 16.2% in males and 11.70 % in females 5 . FTO gene has nine exons and many single-nucleotide polymorphisms (SNPs) 6 which is located on chromosome 16 (16q12.2). According to genome-wide association study (GWAS) gene susceptibility of T2DM has common variant rs9939609 in the FTO gene that influences Asian populations for diabetes 7 .…”