Allele and genotype frequency of a genetic variant in ataxia telangiectasia mutated gene affecting glycemic response to metformin in South Indian population

Abstract

Allele and genotype frequency of a genetic variant in ATM gene affecting glycemic response to metformin in South Indian population.Context:The novel polymorphism in ATM gene (rs11212617), which is implicated to have association with metformin response, exhibits inter-ethnic variability in the allele and genotype frequency distribution.Aims and Design:The objective of the present study is to establish the allele and genotype frequency of rs11212617 single nucleotide polymorphism in ATM gene, in South Indian population and to find if this variant has any role in the etiology of type 2 diabetes mellitus.Materials and Methods:The study was performed in 2 cohorts of populations, 112 healthy volunteers and 118 type 2 diabetes mellitus patients. Genomic deoxyribonucleic acid (DNA) was extracted from peripheral blood leucocytes by phenol-chloroform method and genotyping was performed by real-time polymerase chain reaction using TaqMan assay.Results:In South Indian population, the frequency of major A allele was 0.65 and the minor C allele was 0.35. AA and CC are the homozygous genotypes with frequency of 0.39 and 0.09 respectively. The frequency of heterozygous genotype AC (0.52) was found to be higher than the homozygotes. There was no significant difference in the frequency distribution in the diabetic population, which implies that this variant does not have any causative role in the disease etiology. The frequency distributions were found to be significantly different from the distributions in other ethnic populations such as Caucasians, Chinese, Japanese and Africans. But there was no significant difference when compared with the Gujarati Indians of Houston.Conclusion:The frequency distribution of this novel variant in South Indian population forms a framework for further gene disease association studies to establish the association of this variant with metformin response. Our study could not find any association of this variant with respect to the disease etiology.

Pharmacogenetics of Type 2 Diabetes—Progress and Prospects

“…An additional meta-analysis, performed in combination with data from the previously described GoDARTS and UKPDS, achieved the level of statistical significance (combined OR of 1.25, 95% CI 1.13–1.38, p = 7.8 × 10 −6 ) [ 21 ]. Subsequently, no significant difference between response to metformin in patients with T2D and rs11212617 was observed in a set of studies [ 44 , 45 ]. The inconsistency between the different studies can be assumed to be resulted both from the features of the cohort—its ethnic composition, samples size as well as approaches used to patients’ selection and examination.…”

A Protocol for the Study of Polymorphisms and Response to Metformin in Patients with Type 2 Diabetes in Trinidad

“…[17][18][19] Polymorphisms in non-transporter genes, such as the ATM gene (associated with DNA repair and cell cycle control), also affect the clinical response to metformin. [20][21][22]…”

Phenotypic and genetic characteristics of patients with type 2 diabetes with different responses to metformin therapy in Novosibirsk region

“…на жителях Южной Индии (118 пациентов с СД2 и 112 здоровых) оценивали связь полиморфного локуса rs11212617 с развитием СД2. Однако влияния данного полиморфного локуса на предрасположенность к СД2 не выявили: OR=1,09, 95% CI=0,75-1,60 [19].…”