Human chromosome 17 in essential hypertension.
ABSTRACT Hypertension affects up to 30% of the adult population in Western societies and is a major risk factor for kidney disease, stroke and coronary heart disease. It is a complex trait thought to be influenced by a number of genes and environmental factors, although the precise aetiology remains unknown at this time. A number of methods have been successfully used to identify mutations that cause Mendelian traits and these are now being applied to the investigation of complex diseases. This review summarises the data gathered, using such approaches, that suggest there is a gene or genes on chromosome 17 causing human essential hypertension. Studies in rodent models are discussed first, followed by studies of human hypertension that include the investigation of pseudohypoaldosteronism type II, a monogenic trait that manifests with hypertension alongside other phenotypic variables. In addition, candidate gene studies, genome screens and linkage studies based on comparative mapping are outlined. To date no gene has been identified on human chromosome 17 that influences blood pressure and causes human essential hypertension. However, results of ongoing fine mapping and candidate gene studies in both rodents and man are eagerly awaited.
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ABSTRACT: The polygenic nature of essential hypertension and its dependence on environmental factors pose a challenge for biomedical research. We hypothesized that the analysis of gene expression profiles from peripheral blood cells would distinguish patients with hypertension from normotensives. In order to test this, total RNA from peripheral blood cells was isolated. RNA was reversed-transcribed and labeled and gene expression analyzed using significance Analysis Microarrays (Stanford University, CA, USA). Briefly, Significance Analysis Microarrays (SAM) thresholding identified 31 up-regulated and 18 down-regulated genes with fold changes of ≥2 or ≤0.5 and q-value≤5% in expression. Statistically significantly gene ontology (GO) function and biological process differentially expressed in essential hypertension were MHC class II receptor activity and immune response respectively. Biological pathway analysis identified several related pathways which are associated with immune/inflammatory responses. Quantitative Real-Time RT-PCR results were consistent with the microarray results. The levels of C-reactive protein were higher in hypertensive patients than normotensives and inflammation-related genes were increased as well. In conclusion, genes enriched for "immune/inflammatory responses" may be associated with essential hypertension. In addition, there is a correlation between systemic inflammation and hypertension. It is anticipated that these findings may provide accurate and efficient strategies for prevention, diagnosis and control of this disorder.International journal of medical sciences 01/2011; 8(2):168-79. · 2.07 Impact Factor
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ABSTRACT: Phenylethanolamine N-methyltransferase gene (PNMT) catalyzes the synthesis of epinephrine and plays an important role in regulating cardiovascular function. Genetic variation in the PNMT promoter is reportedly associated with the risk of essential hypertension in certain population. In the present study, we explored the association of two common PNMT promoter single-nucleotide polymorphisms (SNPs) G-367A (rs3764351) and G-161A (rs876493) and their haplotypes with the risk of essential hypertension in a Han Chinese population, using 316 pairs of age-, sex-, and geographically matched essential hypertension patients and normotensive controls. No significant difference in allele and genotype frequencies at either G-367A (rs3764351) or G-161A (rs876493) was observed between essential hypertension patients and normotensive controls. However, the 2-SNP AA haplotype was found significantly more common in normotensive controls than in essential hypertensive patients (P = 0.01; adjusted odds ratios, 0.17; 95% confidence interval, 0.05-0.58). The 2-SNP AA haplotype in the PNMT promoter is associated with decreased risk of essential hypertension in Han Chinese. This is the first evidence of an association between a PNMT promoter haplotype and the risk of essential hypertension.American Journal of Hypertension 08/2011; 24(11):1222-6. · 3.67 Impact Factor
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ABSTRACT: OBJECTIVES: The Golgi SNAP Receptor Complex Member 2 (GOSR2) gene is a Golgi-associated soluble factor attachment receptor (SNARE) protein involved in intra-Golgi protein trafficking on chromosome 17q21, which is the hypertension linkage peak on the human chromosome. The aim of the present study was to assess the association between the human GOSR2 gene and essential hypertension (EH) using a haplotype-based case-control study. METHODS: A total of 320 EH patients and 205 age-matched controls were genotyped for the five single-nucleotide polymorphisms (SNPs) used as genetic markers for the human GOSR2 gene (rs197932, rs3785889, rs197922, rs17608766, and rs16941382). Data were analyzed for three separate groups: the total subjects, men, and women. RESULTS: The overall distribution of the haplotypes in men was significantly different between the EH patients and the control subjects (P=0.002). Additionally, the frequency of the T-A-G haplotype (rs197932-rs3785889-rs197922) for men was significantly higher in the EH patients than in the control subjects (P=0.049). After adjustment for the major risk factors, multiple logistic regression analysis also revealed that the frequency of men with the T-A-G haplotype (homozygous and heterozygous diplotypes) was significantly higher than that in men without the haplotype (OR=1.756, P=0.039). CONCLUSIONS: The results of this study indicate that the T-A-G haplotype may be a useful genetic marker for EH in Japanese men.Clinical biochemistry 01/2013; · 2.02 Impact Factor