Mitochondrial and nuclear gene mutations in the type 2 diabetes patients of Coimbatore population

Abstract

Involvement of mitochondrial and nuclear gene mutations in the development of type 2 diabetes (T2D) has been established well in various populations around the world. Previously, we have found the mitochondrial A>G transition at nucleotide position 3243 and 8296 in the T2D patients of Coimbatore population. This study is aimed to screen for the presence of various mitochondrial and nuclear DNA mutations in the T2D patients of Coimbatore to identify most prevalent mutation. This helps in identifying the susceptible individuals based on their clinical phenotype in future. Blood samples were collected from 150 unrelated late-onset T2D patients and 100 age-matched unrelated control samples according to World Health Organization criteria. Genotyping for the selected genes was done by polymerase chain reaction-single strand confirmation polymorphism, direct sequencing, and polymerase chain reaction-restriction fragment length polymorphism. The mitochondrial T>C transition at 8356 and nuclear-encoded GLUT1 gene mutation were found in the selected T2D patients. The T8356C mutation was found in two patients (1.3%), and the clinical characteristics were found to be similar in both the patients whereas GLUT1 gene mutation was found in seven patients. Four out of seven patients showed homozygous (-) genotype and three patients showed heterozygous (±) genotype for the mutant allele XbaI. Among these three patients, one patient was found to have elevated level of urea and creatinine with the history of kidney dysfunction and chronic T2D. Our results suggest that the T8356C and GLUT1 gene mutations may have an important role in developing late-onset T2D in Coimbatore population. Particularly, individuals with GLUT1 gene may develop kidney dysfunction at their later age.

Association between glucose transporter 1 rs841853 polymorphism and type 2 diabetes mellitus risk may be population specific (葡萄糖转移酶1的rs841853基因多态性与2型糖尿发生风险的关系可能具有人群特异性)

“…In Caucasians, the T allele prevalence in the control and T2DM groups was 32.1% and 37.8%, respectively; in Asians, the prevalence of the T allele in the control and T2DM groups was 15.0% and 22.0%, respectively, and it Blacks it was 52.2% and 42.0%, respectively. Furthermore, the genotype distribution in one article was not in HWE ( P < 0.05) …”

“…The combined search yielded at least 197 references. After discarding references with overlapping data and those that obviously did not meet the selection criteria, 14 relevant case control or cohort studies were included . Four of these 14 articles contained subjects from two or three different ethnic groups .…”

“…Glucose transporter 1 ( GLUT1 ), initially characterized as the erythrocyte glucose transporter, has been examined by several groups as a candidate gene that may confer susceptibility to T2DM. However, previous studies that investigated the association between the GLUT1 rs841853 polymorphism and T2DM have so far provided inconclusive or contentious results . For T2DM, the rs841853 polymorphism has been reported to be either a risk factor, neutral, or even a protective factor for the development of the disease.…”

Mitochondrial complex I and V gene polymorphisms in type II diabetes mellitus among high risk Mizo-Mongoloid population, Northeast India

“…Earlier reports showed the association of mitochondrial DNA mutations like 1310C < T, 1382A < C, 1438G < A, 1201A < G, 3243A < G, 3252A < G, 3256A < T, 3264A < C, 3271A < C, 3290T < C, 3303C < T, 3316G < A, 3394T < C, 8296A < G, 8344A < G, 11778G < A, 12026A < G, 12258C < A, 14577T < C, 14709T < C and 16189T < C [ 16 – 20 ] with T2D development. Particularly, mutation in tRNA Leu gene at 3243 (A < G) position and in the subunits of NADH dehydrogenase 1 and 4 have been reported to have strong association with incidence of diabetes in different populations [ 18 , 19 , 21 , 22 ]. There was a significant correlation between the number of somatic mtDNA ATP6 mutations and the smoking and consuming betel-nut with paan (OR: 3.52; 95 % CI: 0.96–12.11) for the type 2 diabetes along with drinking alcohol (OR: 4.62; 95 % CI: 1.82–14.53).…”

Mitochondrial ND1 gene mutation analysis in type II diabetes of Karaikudi population

“…Mitochondria play an imperative role in glucose metabolism, insulin secretion and biogenesis, hence its dysfunction is reportedly found to play a crucial role in diabetes development (Gerbitz et al 1996;Choo Kang et al 2002). Earlier reports showed the association of mitochondrial DNA mutations like 1310C [T, 1382A[C, 1438G[A, 1201A[G, 3243A[G, 3252A[G, 3256A[T, 3264A[C, 3271A[C, 3290T[C, 3303C[T, 3316G[A, 3394T[C, 8296A[G, 8344A[G, 11778G[A, 12026A[G, 12258C[A, 14577T[C, 14709T[C and 16189T[C (Giles et al 1980Alcolado et al 1994;Kalinin et al 1995;Seneca et al 1998;Chinnery et al 2000;Hattori et al 2003;Pranoto 2005;Brandon et al 2005;Liu et al 2007;Mezghani et al 2010;Vijaya Padma et al 2010;Duraisamy et al 2010;Weng et al, 2013) with T2D development. Particularly, mutation in tRNA Leu gene at 3243 (A[G) position and in the subunits of NADH dehydrogenase 1 and 4 have been reported to have strong association with diabetes incidence in different populations (Kalinin et al 1995;Zhao and Zhang 2001;Lam et al 2001;Pranoto 2005;Yu et al 2004;Duraisamy et al 2010;Vijaya Padma et al 2010).…”