Association between rs20456 and rs6930913 of Kinesin-Like Family 6 and Hypertension in a Chinese Cohort.

This study aimed to investigate the relationship between kinesin-like family 6 (KIF6) polymorphisms and hypertension in a northeast Chinese cohort. In this study, two single nucleotide polymorphisms of KIF6 (rs20456 and rs6930913) and their haplotype were analyzed in 382 hypertension patients and 378 controls with SHEsis analysis platform, and the gene-environmental interactions were evaluated with logistic regression analysis. After adjusting for confounding factors, significantly lower risk of hypertension was observed in participants with genotype TC (0.416 (CI 0.299-0.578), p < 0.001) and CC (0.577 (0.389-0.857), p=0.007) of rs20456 compared with TT. For rs6930913, allele T (0.522 (0.386-0.704), p < 0.001), genotype TT (0.325 (0.205-0.515), p < 0.001), and genotype CT (0.513 (0.379-0.693), p < 0.001) were significantly associated with lower risk of hypertension than allele C and CC genotype, respectively. Gene-environment analyses confirmed the significant influence on hypertension by the interactions between genotypes distribution in rs20456 (CT: p=0.036, TT: p=0.022) and smoking status. No interactions were found between smoking and rs6930913, except those with dominant or recessive genetic models (both P s =0.006). There were no interactions between KIF6 and overweight (all P s > 0.05). Haplotype analyses showed that CC (p=0.005) and TC (p=0.001) of rs20456 and rs6930913 were significantly associated with a statistically increased risk of hypertension. The false-positive report probability (FPRP) analysis was used to verify significant findings. In conclusions, KIF6 might affect the susceptibility of hypertension. The allele C (rs20456) and allele T (rs690913) were inclined to protect individuals from hypertension both in genotype and haplotype analyses.

Association of rs2271037 and rs3749585 polymorphisms in CORIN with susceptibility to hypertension in a Chinese Han population: A case-control study.

Corins are membrane-bound protease that regulates blood pressure by activating the natriuretic peptides. These pro-atrial natriuretic peptide convertases are essential for sodium homeostasis and normal blood pressure. CORIN variants have been identified in humans and other animals, but no studies of CORIN polymorphisms have been conducted in northeastern China. This study aims to investigate the association of 2 single nucleotide polymorphisms (SNPs) in CORIN (rs2271037 and rs3749585) with hypertension, as well as their potential interactions with some risk factors of hypertension in a Han population of northeastern China. A case-control study, including 402 patients with hypertension and 406 participants with normal blood pressure, was conducted in Liaoning province. SNP genotyping was carried out by high resolution melting (HRM) after polymerase chain reaction amplifications. Since rs3749585 is located in 3' untranslated region (UTR) of CORIN, in silico analysis was used to predict target micro RNAs on TargetScan, miRanda, and DIANA-microT. As a result, mutant T allele in rs2271037 (odds ratio [OR], 1.693; 95% confidence [CI], 1.528-1.877; p < 0.001) and C allele in rs3749585 (OR, 1.114; 95% CI 1.011-1.227; p = 0.029) increased the risk of hypertension, comparing with wild G allele and T allele, respectively. Patients with genotype TT (OR, 10.209; 95% CI, 6.414-16.250; p < 0.001) and GT (OR, 1.730; 95% CI, 1.226-2.443; p = 0.002) have higher risk of hypertension than those with genotype GG. SNP rs2271037 was significantly associated with susceptibility to hypertension in all genetic models (dominant model: OR, 2.879; 95% CI, 2.080-3.986; p < 0.001; recessive model: OR, 7.159; 95% CI, 4.779-10.724; p < 0.001; additive model: OR, 1.535; 95% CI, 1.163-2.027; p = 0.002). SNP rs3749585 was significantly correlated with hypertension susceptibility only in dominant model (OR, 1.533; 95% CI, 1.073-2.189; p = 0.019), but not in recessive model (OR, 1.220; 95% CI, 0.906-1.644; p = 0.191) or additive model (OR, 0.915; 95% CI, 0.694-1.205; p = 0.527). After adjusting for age, gender, body mass index (BMI), smoking, low-density lipoprotein cholesterol, and serum sodium level in logistic models, the same statistical results were obtained. Interaction study showed the association between CORIN polymorphisms and hypertension could be changed by overweight (BMI ≥ 25 kg/m2). In silico analyses implicated hsa-miR-495 as a target miRNA that potentially interacts with the 3' UTR of CORIN. In conclusion, polymorphisms of rs2271037 and rs3749585 in CORIN were significantly associated with hypertension in a Han population of northeastern China. The mutant-type T allele of rs2271037 and C allele of rs3749585 might increase the susceptibility to hypertension in this population.

Association of tag SNPs of GPx-3 with essential hypertension in rural Han Chinese in Fuxin, Liaoning, China.

BACKGROUND: Genetic mechanisms contribute to blood pressure regulation. This study investigated whether glutathione peroxidase (GPx-3) tag single nucleotide polymorphisms (SNPs) are associated with hypertension in the rural areas of Fuxin county, Liaoning province, China. METHODS: Indigenous Fuxin Han people participated, 523 unrelated hypertensives and 547 controls were recruited. All tag SNPs of GPx-3 gene were selected. We estimated SNP allele frequency in DNA pools with pyrosequencing. RESULTS: Before Bonferroni correction, C allele frequency for rs8177417 was significantly higher in hypertensives than those in controls (23.4% vs. 19.3%, P = 0.014); T allele frequency for rs3828599 was significantly lower in hypertensives than those in controls (35.6% vs. 40.8%, P = 0.009). However, when a Bonferroni correction for multiple testing was applied, only the polymorphisms rs3828599 of GPx-3 gene was associated with hypertension (P = 0.045, OR: 0.833, 95%CI: 0.695 - 0.998). CONCLUSION: The polymorphism of rs3828599 of GPx-3 gene might be associated with hypertension in rural Han Chinese from Fuxin, Liaoning.

Escherichia coli induces apoptosis in human monocytic U937 cells through the Fas/FasL signaling pathway.

Apoptosis is a genetically regulated cellular suicide mechanism that plays an essential role in development and in defense of multicellular organism. Escherichia coli (E. coli) can induce monocyte apoptosis; however, the mechanism is not clear. This study determines if Fas/FasL regulates E. coli-induced human monocyte line U937 cell apoptosis. We found that infection of U937 cells with E. coli induced rapid cell death in a dose- and time-dependent manner displaying the characteristic features of apoptosis. Moreover, opsonized E. coli induced U937 apoptosis with a higher apoptotic rate (53.29 ± 5.83%) than non-opsonized E. coli (19.37 ± 2.56%). Studying the underlying mechanisms we found that the E. coli-induced apoptosis was associated with a more prominent induction expression of Fas/FasL in a time- and dose-dependent manner. Furthermore, E. coli treatment resulted in a significant increase in the levels of DR5, TRAIL, and FADD, but exerted no statistically significant effects on the levels of DR4. The activity of caspase-8 enzyme increased in infection groups, positively correlated with apoptosis rate. Taken together, these results clearly indicate that receptor-mediated phagocytosis of E. coli induces apoptosis. Moreover, our findings suggest a possible regulatory role of Fas/FasL in the pathway of E. coli infection.