Renin-Angiotensin System Gene Polymorphisms and Hypertension.

Hypertension has emerged as a major public health problem in developing countries including India. Hypertension, a major cardiovascular risk factor is recognized as a multi-factorial trait resulting from the interaction of various environmental and genetic factors. The genetic contribution is speculated to make 30% to 40% of the variation in blood pressure. Identification of variant genes that contribute to the development of hypertension is further complicated because the cardiac output and peripheral resistance, are controlled by other intermediary phenotypes. Sodium has been postulated as the major intermediary in blood pressure regulation. Therefore, polymorphisms of candidate genes encoding proteins influencing renal tubular sodium transport, either directly or indirectly through effects on intra-renal hemodynamics, have been associated with differences in blood pressure level. Considering the importance of genetics on hypertension and the diversity of the related genes, evaluation of these genes and the study of new genes are necessary. It is hoped that by deducting related genes for essential hypertension in individual, will help in prevention of potential patients. We will be able to diagnose those at risk and develop new treatments for these patients.

Robertsonian translocation T (21; 21) in a female born to normal parents: a case report.

Downs syndrome (DS) occurs due to an extra copy of chromosome 21. About 3% of cases of Downs syndrome occur due to Robertsonian translocation, most commonly t (14; 21), other types of translocations are very rare cause of the syndrome. A 10-year-old patient with mental retardation was admitted following road traffic accident. Patient had flabby muscles, had delayed mile stones, stunted growth for the age, slanting of eyes, flat nasal bridge, and ineligible speech. On cytogenetic analysis the patient had karyotype showing one normal chromosome 21 and one Robertsonian translocation t (21; 21). Parents and siblings of the patient were phenotypically normal. Robertsonian translocation t (21; 21), can occur by transmission from carrier parent, due to ovarian mosaicism for Robertsonian translocation or may appear de novo. In the present case as the parents had normal karyotype and siblings were phenotypically normal, Robertsonian translocation probably have arisen de novo. The present case was a case of Downs syndrome with Robertsonian translocation t (21;21) probably arising de novo.

Endothelial nitric oxide synthase gene polymorphisms and the risk of hypertension in an Indian population.

Genetic variants of eNOS gene play a significant role in the pathogenesis of hypertension. Many environmental factors have, also, been implicated in the aetiology of hypertension. We carried out an age-matched case-control study among adults. Hypertension was defined according to JNC-VII criteria and eNOS gene polymorphisms were determined by PCR and PCR followed by PCR-RFLP. eNOS intron 4 aa genotype (adjusted OR 6.81; 95% CI 2.29-20.25) and eNOS 894TT genotype (adjusted OR 7.84; 95% CI 2.57-23.96) were associated with the risk of hypertension. Tobacco users (either smoking/chewing or both) with eNOS intron 4 aa genotype (OR 14.00: 95% CI 1.20-163.37), eNOS 894GG genotype (OR 5.56: 95% CI 3.72-8.31), and eNOS T-786C CC genotype (OR 9.00: 95% CI 1.14-71.04) were at an increased risk of hypertension. Similarly a significant gene-environment interaction was observed between individuals consuming alcohol with eNOS intron 4 aa genotype (OR 12.00: 95% CI 1.20-143.73) and eNOS 894GG genotype (OR 1.95: 95% CI 1.35-2.81). The present study identified few susceptible genotypes of the eNOS gene with the risk of hypertension. Moreover, the interactive effects between the environmental factors and the risk of hypertension were dependent on the eNOS genotypes.

Population attributable risk estimates for risk factors associated with hypertension in an Indian population.

BACKGROUND: Little evidence exists regarding the magnitude of contribution of risk factors associated with hypertension in India. Determination of potentially modifiable risk factors is necessary to focus prevention strategies. DESIGN: Age-matched case-control study. METHODS: A total of 350 hypertensive cases and 350 controls of both sexes in the age group 20-65 years. Hypertension was defined according to JNC VII criteria. Adjusted odds ratio (OR) and population attributable risk percentage (PAR %) for hypertension were calculated. RESULTS: In multivariate analysis, tobacco users (either tobacco chewing/smoking or both) (adjusted OR 5.1, 95% CI 3.6-7.3), tobacco chewing (adjusted OR 3.2, 95% CI 2.2-4.6), smoking (adjusted OR 2.9, 95% CI 1.9-4.4), and alcohol consumption (adjusted OR 1.5, 95% CI 1.1-2.2) was the strongest determinants of hypertension. A dose-response relation was found between the number of cigarettes smoked per day (χ2 for trend = 26.07; p < 0.0001) and the amount of alcohol consumption per day (χ2 for trend = 24.26; p < 0.0001) and the risk of hypertension. PARs were 70.3% (95% CI 63.0-77.5) for tobacco use, 45.3% (95% CI 37.1-53.4) for tobacco chewing, 31.5% (95% CI 21.3-40.9) for smoking, and 33.6% (95% CI 22.9-44.4) for alcohol consumption. CONCLUSION: Our results indicate that incident hypertension cases are largely attributable to the habit of tobacco use and alcohol consumption. Therefore, changing these selected lifestyle factors needs to be prioritized as a major strategy for reducing incidence of hypertension in our population.

Glutathione S-transferase M1 and T1 gene polymorphisms and risk of hypertension in tea garden workers of North-East India.

AIMS: Polymorphisms of genes encoding phase II metabolic enzymes, for example, glutathione S-transferase, have been linked with hypertension. The present study aimed at finding out the association between GSTM1 and GSTT1 polymorphism and hypertension in a population from North-East India. MATERIALS AND METHODS: We carried out a case-control study in tea garden workers of Assam. A total of 223 hypertensive cases and 236 normotensive control subjects were recruited with a record of socio-demographic information, blood pressure, and anthropometric data. Fasting venous blood samples from all subjects were obtained and subjected to DNA extraction and polymerase chain reaction to detect polymorphism of the GSTM1 and GSTT1 genes. RESULTS: The null genotype was prevalent in 38.1% and 28.1% of the study participants (cases and controls) for GSTM1 and GSTT1 genes, respectively. Hypertensive subjects had a significantly higher prevalence of the GSTM1 null genotype (43% vs. 33.5%, than normotensive control subjects, p=0.035). Association between the GSTM1 null genotype and hypertension was significant in younger subjects. Tobacco users with the GSTT1 null genotype were at an increased risk for hypertension. CONCLUSION: The knowledge of GSTM1 and GSTT1 variant status will be useful to predict the risk of hypertension in a population.

Prevalence of endothelial nitric oxide synthase (eNOS) gene exon 7 Glu298Asp variant in North Eastern India.

BACKGROUND & OBJECTIVES: Endothelial nitric oxide is a potent vasodilator and impairment of its generation brought about by gene polymorphism is considered a major predictor for several diseases. A single nucleotide polymorphism G894T within exon 7 of endothelial nitric oxide synthase (eNOS-7) gene, resulting in a replacement of glutamic acid by aspartic acid, has been studied as a putative candidate gene for cardiovascular diseases. The pattern of eNOS-7 Glu298Asp variant in the Indian population is poorly known. The present study was planned to determine the prevalence of the variant of this gene among tea garden community in Assam, North-East India with high prevalence of hypertension. METHODS: Study participants of both sex aged ≥18 yr were recruited randomly from temporary field clinics established in tea gardens of Dibrugarh, Assam. Genomic DNA was extracted from 409 subjects by the conventional phenol-chloroform method. The prevalence of the eNOS exon 7 Glu298Asp variant was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: The study population was in Hardy-Weinberg Equilibrium. The frequency of the eNOS GG, GT and TT genotypes was found to be 75, 22 and 3 per cent respectively and did not show any significant difference in gender wise analysis. INTERPRETATION & CONCLUSIONS: Our results showed that the prevalence of the homozygous GG genotype was high (75%) and the rare mutant genotype (homozygous, TT) was 3 per cent in a population at risk with cardiovascular disease. Such population-based data on various polymorphisms can ultimately be exploited in pharmacogenomics.