Type 2 Diabetes Mellitus and the Association of Candidate Genes in Asian Indian Population from Hyderabad, India

Khan, Imran Ali; Poornima, Subhadra; Jahan, Parveen; Rao, Pragna; Hasan, Qurratulain

doi:10.7860/jcdr/2015/14471.6855

Cited by 26 publications

(21 citation statements)

References 34 publications

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“…The study results revealed that the percentage prevalence of the rs7903146 TCF7L2 SNP, followed by the rs12255372 was relatively higher in the T2DM participants and is in conjunction with other earlier reports that investigated the prevalence of these SNPs. 1,2,15,16 Mechanistic studies addressing the presence and association of these polymorphisms in the risk of incidence of T2DM highlight that carriers of the SNPs exhibit modulations in glucagon and insulin secretion, oral glucose tolerance, leptin regulation and adipose tissue metabolism. 1,8,9,17 In order to understand the risk of incidence of T2DM in the non-diabetic controls (mean age 26.15±1.4) of the present study we carried out an OGTT and similar to other earlier reports, the present data also indicates that the risk allele carriers exhibited relatively higher plasma glucose levels, thus indicating that proper counseling, dietary interventions and physical exercise could play a vital role in the preventive management of T2DM.…”

Section: Discussionmentioning

confidence: 99%

“…T2DM specific linkage and functional studies pinpoint that the transcription factor 7-like 2 (TCF7L2) Wnt pathway regulatory gene located in chromosome 10q25.3, plays an important role in islet cell survival, proliferation, regeneration, synthesis of the incretin GLP-1 (glucagon like peptide-1), lipid and glucose metabolism and is strongly associated with the risk of incidence of T2DM. [2][3][4][5][6][7] The rs7903146, rs12255372 intronic variants of the TCF7L2 gene are reported to functionally impair glucagon, insulin, incretin secretions; impair glucose regulation, tolerance and modulate body mass index (BMI). 8,9 While population specific studies on the association of TCF7L2 with T2DM in regions of North India, Chennai and Hyderabad exists, the prevalence and distribution of these allelic variants in south Tamil Nadu has been obscure.…”

Section: Introductionmentioning

confidence: 99%

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Pilot studies on the prevalence and association of TCF7L2 polymorphisms in non-diabetic participants and type 2 diabetic patients of South Tamil Nadu

Ramanathan¹,

Murugan²,

Velayutham³

et al. 2019

Int J Community Med Public Health

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Background: Genetic predisposition plays a critical role in the incidence of type 2 diabetes mellitus (T2DM). While a few reports strongly associate TCF7L2 gene polymorphisms in the T2DM incidence in India, data pertaining to the prevalence of these polymorphisms in the south Tamil Nadu population has been lacking. Hence, the present study aims to determine the prevalence and association of the TCF7L2 gene variants rs7903146, rs12255372 in the regional population of south Tamil Nadu.Methods: Peripheral blood samples from controls, T2DM patients were utilized to isolate genomic DNA and genotyping was carried out using PCR based strategies, direct sequencing. Socio-demographic details, anthropometric measurements, determination of postprandial, random blood glucose levels and oral glucose tolerance test (OGTT) were further carried out to evaluate the predisposition risk for T2DM.Results: 50% of the control group participants and 73.9% of the T2DM patients were positive (CT/TT) for the TCF7L2 polymorphism rs7903146. The rs12255372 SNP was less prevalent in the controls, patients and was dispersed in only 25% of the controls and 60.9% (GT/TT) of the patients. The 60 minutes plasma glucose levels for the oral glucose tolerance test (OGTT) was higher (143.3±19.8) in the rs7903146 and rs12255372 positive control participants.Conclusions: The study results reveal that TCF7L2 polymorphisms are dispersed in the regional population and further large scale, long term follow up studies will aid preventive and therapeutic measures in T2DM.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pilot studies on the prevalence and association of TCF7L2 polymorphisms in non-diabetic participants and type 2 diabetic patients of South Tamil Nadu

Ramanathan¹,

Murugan²,

Velayutham³

et al. 2019

Int J Community Med Public Health

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“…Weight (kg)/height (m 2 ) metrics were used to calculate body mass index (BMI). Serum samples were used to measure fasting blood sugar (FBS), postprandial blood glucose (PPBS), glycosylated hemoglobin (HbA1C) and lipid profile; total cholesterol (TC), triglycerides (TG), high‐density‐lipoprotein‐cholesterol (HDL‐C) and low‐density lipoprotein‐cholesterol (LDL‐C) . Homeostasis model assessment for insulin resistance (HOMA–IR) was calculated to evaluate IR status using the formula; glucose (mmol/L) X insulin (lIU/mL)/22.5.…”

Section: Methodsmentioning

confidence: 99%

“…Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by increased insulin resistance and impaired insulin secretion by pancreatic β‐cells . The well‐known risk factors involved in the development of diabetes and allied complications are a persistent increase in insulin resistance, visceral adiposity, full of fat diet, sedentary lifestyle and genetic composition .…”

Section: Introductionmentioning

confidence: 99%

Distribution of CYP2C8 and CYP2C9 amino acid substitution alleles in South Indian diabetes patients: A genotypic and computational protein phenotype study

Rao

Murthy

Shaik

et al. 2017

Clin Exp Pharma Physio

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The CYP2C8 and CYP2C9 are two major isoforms of the cytochrome P450 enzyme family, which is involved in drug response, detoxification, and disease development. This study describes the differential distribution of amino acid substitution variants of CYP2C8 (*2-I269F & *3-R139K) and CYP2C9 (*2-C144R & *3-L359A) genes in 234 type 2 diabetes mellitus (T2DM) patients and 218 healthy controls from Andhra Pradesh, South India. Single locus genotype analysis has revealed that homozygous recessive genotypes of 2C8*2-TT (P ≤ .03), 2C9*2-TT (P ≤ .02), and heterozygous 2C9*3-AC (P ≤ .006) are seen to be increasingly present in the case group, indicating a significant level of their association with diabetes in Andhra population. The statistical significance of these recessive genotypes has persisted even under their corresponding allelic forms (P ≤ .01). Genotype association results were further examined by computational protein structure and stability analysis to assess the deleteriousness of the amino acid changes. The mutant CYP 2C8 and 2C9 (both *2 and *3) proteins showed structural drifts at both amino acid residue (range 0.43Å-0.77Å), and polypeptide chain levels (range 0.68Å-1.81Å) compared to their wild-type counterparts. Furthermore, the free energy value differences (range -0.915 to -1.38 Kcal/mol) between mutant and native protein structures suggests the deleterious and destabilizing potential of amino acid substitution polymorphisms of CYP genes. The present study confirms the variable distribution of CYP2C8 (*2 and *3) and CYP2C9 (*2 and *3) allelic polymorphisms among South Indian diabetic populations and further warrants the serious attention of CYP gene family, as a putative locus for disease risk assessment and therapy.

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“…The abnormal function of pancreatic beta cells and their loss of secretion of insulin are the main reasons for the progress of the disease [1]. Environmental and genetic factors play a crucial role in causing type 2 diabetes mellitus [2]. Numerous genes are involved in the development of type 2 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Polymorphism Study on SLC30A8 and Its Association with Type 2 Diabetes

Vignesh¹,

Sangeetha²,

Varsha³

2016

Recent Advances in Biology and Medicine

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Type 2 diabetes mellitus (T2DM) is one of the threatening disorders in the world. It affects people of all ages. Type 2 diabetes mellitus is a condition in which the glucose level in the blood is elevated due to improper function of the secretion of insulin from beta cells of the pancreas. It is a multifactorial disease because it is caused by both environmental and hereditary factors. One of the genes which play an important role in type 2 diabetes mellitus is SLC30A8 which encodes for zinc transporter ZnT8. The common polymorphic site for SLC30A8 is rs13266634. This single-nucleotide polymorphism leads to type 2 diabetes mellitus by replacing the arginine residue with tryptophan residue. This review mainly focuses on the polymorphic studies in the gene SLC30A8 and its association with type 2 diabetes mellitus.

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Type 2 Diabetes Mellitus and the Association of Candidate Genes in Asian Indian Population from Hyderabad, India

Cited by 26 publications

References 34 publications

Pilot studies on the prevalence and association of TCF7L2 polymorphisms in non-diabetic participants and type 2 diabetic patients of South Tamil Nadu

Pilot studies on the prevalence and association of TCF7L2 polymorphisms in non-diabetic participants and type 2 diabetic patients of South Tamil Nadu

Distribution of CYP2C8 and CYP2C9 amino acid substitution alleles in South Indian diabetes patients: A genotypic and computational protein phenotype study

Polymorphism Study on SLC30A8 and Its Association with Type 2 Diabetes

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