Isa, Nizam and Ismail, Abd. Aziz AI-Safi and Mohamed, Mafauzy
(2003)
Analysis of Leptin receptor, Glucocorticoid receptor,B-3
Aderenergic receptor and Tumour Necrosis Factor-a
Gene Polymorphism in Type 2 Diabetes Mellitus in Kelantan Malays.
Analysis of Leptin receptor, Glucocorticoid receptor,B-3 Aderenergic receptor and Tumour Necrosis Factor-a Gene Polymorphism in Type 2 Diabetes Mellitus in Kelantan Malays..
(Submitted)
Abstract
Diabetes is a complex disease with both genetics and environmental
component in the pathogenesis. Progress in the human genetic has allowed a better
understanding in the search for either specific or multiple affliction of the candidate
gene susceptible for the disease. Since the past 3 years studies showed that several
genes including the Leptin receptor, f33-adrenergic receptor, Tumour necrosis factor
alpha (Tnf-a.) and Glucocorticoid receptor have been linked and their polymorphism
associated to diabetes. However, the prevalence involvement and polymorphic
variations differ markedly among the ethnic groups. In this initial project the choice of
these candidate genes markers were selected from the biological pathway likely to
the development and the progression of the NIDDM. Future research will include
other known and related gene susceptible to the disease. The potential role of
identification of these variant not only contribute to better understanding of the
pathogenesis of the disease but it also provide a research tool for the studies to
assess the association of the multiple genetics markers with the disease.
We expect to define the association of these genes polymorphism to the
pathogenesis of diabetes in the local population.
Research Methodology
Subject and control 50 patients clinically confirm as diabetes and attending
the Diabetes Clinics in the HUSM were selected. The clinical characteristics
including sex, age, body mass index, blood pressure measurements and
biochemical analysis of HbA 1 c and fasting blood sugar were analyzed. 50 controls
are normal individual who do not have diabetes. A total 10 ml blood were collectedin the EDTA container from each patients and normal individual for DNA extraction
and further genetic analysis.
Genetic determination Genomic DNA was extracted from the above sample
using standard non-phenol extraction procedure. The genomic DNA were amplified
using specific primers and polymerase chain reaction (PCR) conditions for each
specific gene of interest according to published works with modification. The
Restriction Fragment Length Polymorphism (RFLP) was applied for mutation
analysis. Both PCR and RFLP products were subjected to electrophoresis on either
agarose or polyacrylamide gel for allele identifications.
Statistical analysis The chi-square test was carried out for comparison of the
genotype frequency and level of the variable between the genotype groups was
compared using analysis of variance (ANOVA). P values of less than 0.05 were
considered as statistically significant.Results
From the whole sample studied, genotype frequency for mutant allele in these four
genes are ranging from 8.0% to 29.2%. The highest genotype frequency for mutant
allele is the Pentanucleotide Insertion/Deletion Polymorphism of the 3' -UTR of Leptin
receptor gene (17.0%), followed by Trp64Arg polymorphism of the p3-adrenergic
receptor gene (10.0%), followed by Asn363Ser polymorphism of the Glucocorticoid
receptor gene (4.0%) and the lowest is G-308A polymorphism of the Tumour necrosis
factor alpha (Tnf-a.) gene (3.0°Al). While in normal control samples, the result shows
genotype frequency for mutant genes are 16.0% (Lepr), 7.0% (Tnf-a), 3.0% (GRL)
and 2.0% (~3-AR). All genes are not associated with the incidence of type 2
diabetes in Kelantan Malay subjects (p <0.05).Conclusion
We suggested that all genes are not likely to be the major predispose in the
incidence of type 2 diabetes in Kelantan Malay population except for f33-adrenergic
receptor gene. Future studies should be done to screen for other polymorphism in
same genes and also in other genes which have been reported in other populations
to have significant association with the pathogenesis of type 2 diabetes.
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