Affiliation:
1. Molecular and Human Genetics Lab, Department of Zoology, University of Lucknow, Lucknow-226007,
India
2. Department of Medicine, King George’s Medical University, Lucknow-226003, India
Abstract
Background:
Type 2 diabetes mellitus (T2DM) is a complex metabolic disease
that is caused by insulin dysfunction. It is an output of oxidative stress that results from defective
redox reactions and increased reactive metabolites (RMs) and is neutralized by antioxidant
enzymes. It has been reported that decreased levels of antioxidant enzymes are due
to genetic alterations in the respective genes. Therefore, the present study has undertaken a
genetic analysis of antioxidant genes and their interaction in the family to assess T2DM
risk.
Objective:
This study aimed to investigate the individual susceptibility/risk to T2DM using
antioxidant gene variants and their interactions in family members with a diabetic history.
Methods:
Genotypic analysis of antioxidant genes was done by polymerase chain reactionrestriction
fragment length polymorphism (PCR-RFLP), haplotype analysis, and gene-gene
interactions using statistical tools. Pedigrees were constructed by face-to-face interviews
with members of nine families.
Results:
Genotypes AT (CAT-21A>T), IV (GSTP1+313(105I>V), and CT (GPx1
+599C>T) were found to be frequent in diabetic individuals. For instance, in one family, if
only the mother had diabetes, all siblings were found to have the risk genotypes AT (CAT-
21A>T) and CT (GPx1 +599C>T) with 2.12- and 2.11-folds risk of developing T2DM. The
risk haplotypes, NNV (GSTM1 N>P(Null>Present), GSTT1 N>P(Null>Present),
GSTP1105I>V and TCC (CAT-21A>T, SOD2+47C>T, GPx1+599C>T) were observed in
most of the diabetic individuals and non-diabetics possessing the risk haplotypes manifested
altered BMI.
Conclusion:
The present study suggests that the GSTP1105I>V, CAT-21A>T,
SOD2+47C>T and GPx1+599C>T gene variants can be prognostic biomarkers for the assessment
of T2DM risk in healthy individuals.
Funder
Indian Council of Medical Research
Publisher
Bentham Science Publishers Ltd.
Subject
Genetics (clinical),Pharmacology,Genetics,Molecular Biology,Molecular Medicine