Studies to determine the prevalence of candidate gene polymorphism for hypertension among malays
| dc.contributor.author | Mohd Ghazali, Dzuzaini | |
| dc.date.accessioned | 2015-06-25T08:14:12Z | |
| dc.date.available | 2015-06-25T08:14:12Z | |
| dc.date.issued | 2007 | |
| dc.description.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. | en_US |
| dc.identifier.uri | http://hdl.handle.net/123456789/816 | |
| dc.subject | Candidate gene | en_US |
| dc.subject | Polymorphism | en_US |
| dc.title | Studies to determine the prevalence of candidate gene polymorphism for hypertension among malays | en_US |
| dc.type | Thesis | en_US |
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