Tag polymorphisms of solute carrier family 12 member 3 gene modify the risk of hypertension in northeastern Han Chinese.

Converging evidence suggests that the gene encoding solute carrier family 12 member 3 (SLC12A3) is a logical candidate involved in the underlying cause of hypertension. We therefore selected four tag polymorphisms (rs2304483, rs5804, rs8063291 and rs6499857) from SLC12A3 gene to investigate their individual and interactive associations with hypertension in northeastern Han Chinese. There were 1009 hypertensive patients and 756 normotensive controls. Data were analyzed by Haplo.Stats and multifactor dimensionality reduction (MDR) softwares, and risk estimates were expressed as odds ratio (OR) and 95% confidence interval (95% CI). Overall, there were significant differences in the genotype (P=0.002) and allele (P=0.002) distributions of rs5804 between patients and controls. Compared with the most common haplotype A-C-T-G, haplotype G-C-T-G that was overrepresented in controls (P<0.001) reduced the crude and adjusted risk of hypertension by 36% (OR 0.64; 95% CI 0.50-0.81; P<0.001) and 39% (OR 0.61; 95% CI 0.48-0.79; P<0.001), respectively. Further interaction analyses identified an overall best MDR model including rs5804 and body mass index (P=0.001), which was validated by logistic regression analysis. Taken together, our findings demonstrate a predominant role played by SLC12A3 gene rs5804 in determining hypertension risk among northeastern Han Chinese. Moreover, the interaction of this polymorphism with obesity can enhance risk prediction.

Strong association of methylenetetrahydrofolate reductase gene C677T polymorphism with hypertension and hypertension-in-pregnancy in Chinese: a meta-analysis.

Attempts to associate methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism with hypertension have been extensively evaluated, but mostly in Caucasians. We therefore meta-analysed this polymorphism in association with hypertension and hypertension-in-pregnancy (HIP) among Chinese subjects. A random-effects model was applied irrespective of between-study heterogeneity, which was evaluated by subgroup and meta-regression analyses. Study quality was assessed in duplicate. Publication bias was weighed using Egger's test and funnel plot. Data on 20 qualified studies totalling 4461 Chinese subjects were meta-analysed. In overall allelic/genotypic models, carriers of 677T or 677TT were consistently at significantly increased risk of developing hypertension and HIP. No between-study heterogeneity was identified for all genetic models, with the exception for contrast of allele 677T versus 677C in hypertension association studies (P=0.03), and the dominant contrast in HIP association studies (P=0.025). Both the subgroup and meta-regression analyses indicated that study design was a potential source of between-study heterogeneity. Funnel plot and Egger's test suggested no evidence of publication bias. Taken together, our results supported the notion that carriers of 677T or 677TT were at significantly increased risk of developing hypertension and HIP, but indicated caution in interpreting this result, because the study design made marginal significant contribution to the heterogeneity.

Meta-based evidence for apolipoprotein E epsilon2/epsilon3/epsilon4 polymorphism in association with hypertension among Chinese.

Mounting evidence suggests that hypertension is strongly linked to a variety of lipoprotein metabolism abnormalities. Apolipoprotein E gene (ApoE) is one such candidate with its common ɛ2/ɛ3/ɛ4 polymorphism ranking high in hypertension association. To derive more specific information, we pinpoint our research scope in Chinese to test whether this polymorphism is associated with hypertension via a meta-analysis. Random-effects model was performed irrespective of the between study heterogeneity. Data and study quality were assessed in duplicate. Publication bias was evaluated using the fail-safe number. Overall, 12 studies with 14 study groups totalling 1532 hypertensive patients and 2172 controls were identified. Carriers of ApoE ɛ2 allele had no significant increased risk for hypertension (pooled odds ratio (OR)=1.04; 95% confidence interval (CI): 0.80-1.35; P=0.78), compared with those carrying ɛ3 allele, whereas those with ɛ4 allele had a significant increased risk for hypertension (pooled OR=2.03; 95% CI: 1.61-2.55; P<0.00001). After excluding those with other small nationalities, we observed comparison of ApoE ɛ2 with ɛ3 allele yielded a pooled OR of 0.99 (95% CI: 0.82-1.19; P=0.89) among Han Chinese, and that of ɛ4 with ɛ3 yielded a pooled OR of 1.99 (95% CI: 1.48-2.67; P<0.00001). The fail-safe number at the level of 0.05 supported these significant associations. Taken together, our results expand previous findings and show that ApoE ɛ4 allele is associated with a twofold increased risk of developing hypertension in Chinese.

Meta-based association of the lipoprotein lipase gene S447X variant with hypertension and blood pressure variation.

Association of the lipoprotein lipase (LPL) gene S447X variant with hypertension has been investigated extensively, whereas the results are often irreproducible. We therefore conducted a meta-analysis to examine whether S447X variant was associated with hypertension and blood pressure variation. Case-control reports published in English language and humans were identified from MEDLINE, EMBASE and Web of Science search engines as of 10 December 2009. Fixed-effects model was applied to pool data in the absence of between-studies heterogeneity, and random-effects model otherwise. A total of five studies (960 cases and 1145 controls) for hypertension and four studies (n=2777) for blood pressure were included. Compared with 447SS homogeneous carriers, those with 447X variant had a lower risk of hypertension (odds ratio (OR)=0.78; 95% confidence interval (CI): 0.62-0.98; P=0.03), and this effect reached significance under the fixed-effects model (I(2)=30% and P=0.22). Similarly, compared with 447S allele carriers, those with 447X allele carriers also had a lower risk of hypertension (OR=0.79; 95% CI: 0.64-0.98; P=0.03). In case of pregnancy-induced hypertension, no significance was observed (P>0.05). As for blood pressure association, there was no significant difference between 447X variant and 447SS homogeneous carriers for both systolic and diastolic blood pressure in the whole population, even stratified by gender (P>0.05). The Egger test told no publication bias for all associations. This meta-analysis demonstrated that LPL gene S447X variant was significantly associated with hypertension and showed no obvious relation with pregnancy-induced hypertension and blood pressure variation.

Lack of association between alpha-adducin G460W polymorphism and hypertension: evidence from a case-control study and a meta-analysis.

The past two decades have seen an upsurge in detecting the genetic determinants of hypertension. Thereafter, alpha-adducin gene ranks high and one polymorphism, G460W (rs4961), has attracted special attention. We first performed a case-control study to investigate the association of this polymorphism with essential hypertension among Shanghai residents, and then meta-analyzed all available evidence. A total of 950 subjects were recruited for genetic association study. Genotyping for G460W was conducted using PCR and restriction fragment length polymorphism techniques. Meta-analysis search was limited to articles published in English and studies on humans. Data and study quality were assessed in duplicate. Publication bias was evaluated using the fail-safe number. Our case-control study provided no evidence for the association of G460W with essential hypertension, even under assumptions of three genetic modes of inheritance (P>0.05). The subsequent meta-analysis including 15 studies with 4417 cases and 5716 controls also failed to demonstrate overall this association, even upon stratification by race (Caucasians and Asians). For example, the summary odds ratio (OR) under a random effects model indicated that carriers of 460W allele were 1.09 times more likely to develop hypertension (95% confidence interval (CI), 0.96-1.24; P=0.19) among Asians, whereas a protective effect of this allele was observed in Caucasians (OR, 0.93; 95% CI, 0.73-1.18; P=0.54). The fail-safe number at the level of 0.05 was in favour of our findings. Our case-control study and the following meta-analysis failed to provide evidence for the genetic association of alpha-adducin gene G460W polymorphism with hypertension.

Impaired endothelial function in hypertensive patients with target organ damage.

To evaluate the correlation between endothelial dysfunction and multiple target organ damage (TOD), we measured endothelial function using high-resolution ultrasonography in hypertensive patients with or without TOD. Two hundred and eighty patients with hypertension were divided into four groups as follows: no TOD (Group I, n=61); 1 TOD (Group II, n=113); 2 TOD (Group III, n=59); and >or=3 TOD (Group IV, n=47). Endothelial function was assessed by endothelium-dependent flow-mediated dilatation (FMD) and -independent vasodilation (after sublingual administration of nitroglycerin) of the brachial artery using high-resolution vascular ultrasound. We also assessed the intima-media thickness (IMT) of the common carotid, carotid to femoral pulse wave velocity (cf-PWV) and left ventricular mass index (LVMI). FMD was inversely associated with the number of affected organs. FMD was lower in the patient groups with >or=3 TOD (Group IV: 6.85+/-4.70% vs Group II: 10.00+/-6.15%, P<0.01), 2 TOD (Group III: 7.37+/-5.02% vs Group II, P<0.01) and 1 TOD as compared with patients with no TOD (Group I: 11.88+/-7.11% vs Group II, P<0.05). In univariate correlation analysis, there was a significant relationship between FMD and IMT, serum creatinine, LVMI and cf-PWV. In stepwise multivariate regression analysis, FMD still correlated with waist size (beta=-0.283, P<0.01), age (beta=-0.231, P<0.05) and IMT (beta=-0.197, P=0.05). These findings suggested that reduced FMD was associated with the number of TOD and may be considered an indicator for evaluating TOD.