Studies to determine the prevalence of candidate gene polymorphism for hypertension among malays
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Date
2007
Authors
Mohd Ghazali, Dzuzaini
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Abstract
Hypertension or elevated arterial blood pressure is a substantial public health problem
and is a major risk factor for many common causes of cardiovascular morbidity and
mortality. Blood pressure is regulated by a variety of mechanisms that involve the
products of several genetic loci and a number of environmental factors. "Human
essential hypertension" is a multifactorial disorder that is complicated by the interaction
of both genetic and an environmental factors. Research on the molecular genetics of
human essential hypertension developed several years ago. One approach is to study
candidate genes that may contribute to abnormal blood pressure because of their
known effect on the cardiovascular system.
Among the listed of candidate genes published for their known associations
with hypertension, three of them were selected and their association with hypertension
in the Malays was investigated in this thesis. The prevalence of these polymorphic
variants within the specific candidate genes in the population was also determined.
Polymorphisms studied were the T594M of the epithelial sodium channel (ENaC) gene,
the M235T of the angiotensinogen (AGT) gene and the G894T of the endothelial nitric
oxide synthase (eNOS) gene. A total of 398 DNA samples from 200 hypertensives and
198 age- and sex- matched controls were analyzed in this genetic polymorphism study.
Subjects recruited in this study were pure Malay for three generations.
The frequency distribution of the M235T genotypes in the population was 3.5%
for homozygous wild-type (MM}, 30.4% for heterozygous (MT) and 66.1% for
homozygous mutant (TT). The frequency of the TT genotype was 63.5% in
hypertensives and 68.7% in controls, respectively. The frequencies of the M235 and
T235 alleles were 20.0% and 80.0% among the hypertensives and 17.4% and 82.6%
among the controls. No significant difference was observed in genotype (x2=1.30,
p=0.52) and allele <l=0.87, p=0.35) frequencies among the two study group. The odds
ratio for hypertension is 1.01 for subjects carrying the TT genotype and 0.84 for those
having T allele of the variant.
In contrast, the distribution of genotypes for G894T was 74.1% for homozygous
wild-type (GG), 24.6% for heterozygous (GT) and 1.3% for homozygous mutant (TT),
respectively. Only five individuals from the overall study subjects were found to be
carrying the mutant genotype. When categorized into two groups, it was found that the
frequency of GG, GT and TT were 72.0%, 27.0% and 1.0% in hypertensives and
76.3%, 22.2% and 1.5% in controls. In this study, the frequencies of the G894 and
T894 alleles were 85.5% and 14.5% among the hypertensives and 87.4% and 12.6%
among the controls, respectively. Using chi-square analysis, no significant difference
was observed in genotype (x2=0.94, p=0.33) and allele <l=0.60, p=0.44) frequencies
between both study groups. The odds ratio for hypertension is 1.25 for subjects
carrying the TT genotype and 1.17 for those having allele T of the variants.
In determining the prevalence of T594M polymorphism of the 13-ENaC, it was
found that the overall study subjects are wild-type for this variant. None of the study
subjects carried a homozygous mutant or heterozygous genotype. It is likely that
T594M variant of the 13-ENaC gene is rare among Malay population.
Statistical analysis done using Multiple Linear Regression (MLR) shows that
systolic and diastolic blood pressure were not correlated significantly with !3-ENaC
T594M, AGT M235T and eNOS G894T genotype in both study groups. The genotype
of each variant was not a predictor for both systolic and diastolic blood pressure in the
overall study population. Hence, polymorphic variant of studied candidate genes is not
likely to be a major factor causing hypertension in Malay population.
Keywords: Hypertension, Malays, angiotensinogen gene, epithelial sodium channel
gene, endothelial nitric oxide synthase gene, gene polymorphism.
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Keywords
Candidate gene , Polymorphism