Dongliang Ge

beta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese.

The aim of this study was to investigate the association between polymorphisms in the β2‐adrenergic receptor gene (ADRB2) (−47C/T, Arg16/Gly, Gln27/Glu) and stage‐2 hypertension in northern Han Chinese. We recruited 503 individuals with stage‐2 hypertension and 504 age‐, gender‐, and area‐matched controls from the International Collaborative Study of Cardiovascular Disease in Asia. Genotyping was performed using PCR‐RFLP. Logistic regression analyses revealed that carriers of the Gly16 allele had a significantly higher odds ratio (OR) for hypertension, while carriers of the Glu27 allele had a significantly lower OR. In multivariate linear regression analyses, the Arg16/Gly and Gln27/Glu genotypes were significantly associated with systolic blood pressure level (p= 0.004 and p < 0.001, respectively). In haplotype analyses, we found the frequency of haplotypes composed of the Gly16 and Gln27 alleles was significantly higher, whereas the frequency of haplotypes composed of the Arg16 and Glu27 alleles was significantly lower, in hypertensives compared to their controls (both p= 0.001). These results indicate that the Gly16 and Gln27 alleles of the ADRB2 gene confer an increased risk for stage‐2 hypertension in this northern Han Chinese population.

G Protein β3 Subunit Gene Variants and Essential Hypertension in the Northern Chinese Han Population

Recently a novel C825T polymorphism in the G protein β3 subunit gene was identified that showed an association with hypertension in a German population; the results of studies in other populations have been inconsistent. To examine the contribution of GNB3 polymorphisms to the development of hypertension in the northern Chinese Han population, we conducted a case‐control study consisting of 501 hypertensive cases and 503 controls using the G(‐350)A, C825T and C1429T polymorphisms. Genotypes of samples were determined by PCR and restriction digestion. Single locus analysis showed a significant association between G(‐350)A and hypertension (P = 0.01) but no association for C825T or C1429T. The three polymorphisms were in tight linkage disequilibrium (D′=−1 for G(‐350)A‐C825T, D′= 0.92 for C825T‐C1429T) and a total of 7 haplotypes were observed in the entire population. Haplotype A‐C‐C was found to be significantly related to hypertension (P = 0.032) and A‐C‐C carriers had a more than two‐fold higher risk of hypertension than non‐carriers, after adjustment for BMI and glucose. In conclusion, our study suggests that G(‐350)A is a potential functional polymorphism that may be related to hypertension, whereas the C825T and C1429T polymorphisms are not associated with hypertension in the northern Chinese Han population.

Haplotypic analyses of the aldosterone synthase gene CYP11B2 associated with stage‐2 hypertension in northern Han Chinese

The objective of this study was to investigate the association of polymorphisms in the aldosterone synthase gene CYP11B2 (−344T/C, Lys173/Arg, and an intronic conversion [IC]) with stage‐2 hypertension in northern Han Chinese. A total of 503 hypertensives and their age‐, gender‐, and area‐matched controls were included in this study. The female hypertensives had significantly higher frequencies of the −344T, 173Lys, and IC‐conversion alleles (p = 0.002, 0.002, and 0.014, respectively). The estimated frequency of haplotype composed of the −344T, 173Lys, and IC‐conversion alleles (haplotype 4) was significantly higher in the female hypertensives compared with their controls (p = 0.007). Using a multivariate score test, we found that haplotype 4 remained associated with female hypertension after the adjustment for covariates (p = 0.003), while the haplotype 3 of T‐Arg‐WT showed a protective effect both in the males and in the females (p = 0.03 and 0.006, respectively). The odds ratio for haplotype phase of 4–4 was 2.60 (95% CI, 1.21–5.58) and for 3–3, 0.20 (95%CI, 0.03–0.77). These results indicate that the Lys173 and the IC‐conversion allele of the CYP11B2 gene confer an increased risk for stage‐2 hypertension in northern Han Chinese women.

Lipoprotein lipase gene is in linkage with blood pressure phenotypes in Chinese pedigrees

To elucidate the mechanism of lipid metabolism in the genesis of essential hypertension (EH), we linked blood pressure (BP) phenotypes with the lipoprotein lipase (LPL) gene. Variance component and sib-pair linkage models were used to test the relationship of the polymorphisms in the LPL gene region and EH in 148 Chinese hypertensive families. Linkage evidence with systolic BP (SBP) and diastolic BP (DBP) was observed in a total population of 148 pedigrees with seven flanking microsatellite markers of the LPL gene, with a maximum two-point LOD score of 2.68 and a maximum multipoint LOD score (MLS) of 2.37 for SBP and a maximum MLS of 1.54 for DBP. Suggestive linkage results around this region were also obtained in northern and southern subsets by geographic distribution. In addition, quantitative-transmission/disequilibrium-test analyses showed that there was linkage between DBP and two single nucleotide polymorphisms in the LPL gene. This is the first report of linkage between LPL gene and DBP in the Chinese population. The LPL gene itself might explain our results or the LPL gene region might harbor some genes to explain the observed results to some degree and might contribute to the variation of BP in the Chinese population.

A functional intronic variant in the tyrosine hydroxylase (TH) gene confers risk of essential hypertension in the Northern Chinese Han population

The TH (tyrosine hydroxylase) gene encodes the rate-limiting enzyme of catecholamine biosynthesis, and is involved in the pathogenesis of hypertension, but the relationship of its variants with hypertension has not been extensively studied. We designed a case-controlled study consisting of 503 HT (hypertensive) individuals and 490 NT (normotensive) individuals matched by region, age and gender to systematically investigate the association between the TH gene and hypertension. Based on the HapMap and dbSNP (where SNP is single nucleotide polymorphism) data, four SNPs, rs6356 A>G, rs6357 G>A, rs2070762 T>C and rs1800033 A>G in the TH gene were selected for genotyping. Rs1800033 was not polymorphic in our study population. No significant differences were observed for distributions of rs6356 and rs6357 between the HT and NT groups. However, both the genotype and allele frequencies of rs2070762 showed significant differences between cases and controls (P<0.001 and P=0.005 respectively). In haplotype analysis, a total of eight haplotypes were observed in the entire population and the overall frequency distributions differed significantly between the HT and NT groups. Specifically, haplotype A-A-C (rs6356-rs6357-rs2070762) occurred only in the HT group and A-G-C occurred more commonly in HT subjects than in NT subjects (P=0.003 and P=0.013 respectively). Compared with the most common haplotype A-G-T, the adjusted OR (odds ratio) was 1.83 [95% CI (confidence interval), 1.20-2.79; P=0.0049] for haplotype G-G-C and 20 (P<0.0001) for the haplotype A-A-C. Functional analysis showed that the C allele of rs2070762 functioned as an enhancer in the absence of binding by unidentified transcriptional repressor(s). These results provide evidence for an association of the functional intronic rs2070762 with essential hypertension.

Association analysis of the variant in the regulatory subunit of phosphoinositide 3-kinase (p85α) with Type 2 diabetes mellitus and hypertension in the Chinese Han population

Aims  To determine whether variants in the gene for the regulatory subunit of phosphoinositide 3‐kinase (p85α) are associated with Type 2 diabetes mellitus (Type 2 DM) and hypertension in a Chinese population.