[Strong association between the NINJ2 gene polymorphism and the susceptibility of stroke in Chinese Han population in Fangshan district].

OBJECTIVE: To investigate the association between the NINJ2 gene rs11833579 polymorphism and stroke in Han Chinese population. METHODS: This study was a population-based cross-sectional case-control study. Polymerase chain reaction-restriction fragment length polymorphism (RFLP) and sequencing were used for the detection of NINJ2 genotypes in 790 patients with stroke (679 ischemic stroke) which were Han Chinese population from Fangshan First Hospital and 811 controls which were healthy Han Chinese population without family history of stroke in Fangshan district rural area. RESULTS: In rs11833579 locus of the NINJ2 gene, the frequencies of GG genotype and allele G were higher in ischemic stroke patients than that in controls (P<0.001). The frequency of allele G of the NINJ2 gene was higher in cerebral hemorrhage patients than that in controls (P=0.005). Genotype had little effect on the glucose, total cholesterol and triglyceride. CONCLUSION: There is significant association between rs11833579 site polymorphism of the NINJ2 gene and risk for stroke in Han Chinese population from Fangshan district.

Haplotype-based association of the renin-angiotensin-aldosterone system genes polymorphisms with essential hypertension among Han Chinese: the Fangshan study.

BACKGROUND: Widely evaluated regarding the genetic make-up of essential hypertension are the renin-angiotensin-aldosterone system (RAAS) genes polymorphisms, whereas results are often not reproducible. METHOD: We thus focused on a large Fangshan population to explore association of thirteen polymorphisms in five genes of RAAS. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism and direct sequencing techniques. Data were analyzed using MDR and Haplo.stats programs. RESULTS: All studied polymorphisms satisfied Hardy-Weinberg equilibrium in controls. Three polymorphisms (AGT M235T, ACE I/D and AT1R A1166C) displayed significant differences in the genotype and allele distributions between patients and controls (P < 0.05). Interaction analysis suggested a six-locus model that can be decomposed into three sets of polymorphisms (TaqI and M235T, A-20C and A-6G, I/D and A2350G) each with nonadditive effects. Logistic regression analysis indicated that TaqI [Recessive: crude odds ratio (ORcrude) = 1.47, P = 0.030 and adjusted (ORadjusted) = 1.46, P = 0.050] and I/D (Recessive: ORcrude = 1.40, P = 0.002 and ORadjusted = 1.49, P = 0.002) polymorphisms were significantly and positively associated with the risk of essential hypertension. Under additive and recessive modes of inheritance, similar tendency was observed for M235T polymorphism. Two haplotypes (H6 and H9) were found to significantly reduce essential hypertension risk, whereas after correction only H6 remained significant (OR = 0.25, P = 0.0006). In contrast, haplotype H13 was significantly associated with essential hypertension with a 2.14-2.16-fold increased risk (P < 0.01). Haplotype-phenotype analysis showed significant association of inferred haplotypes with SBP (hap-score = 0.44, simulated P = 0.036). CONCLUSION: Taken together, we demonstrated three two-locus pairs of polymorphisms with synergistic effect out of three genes in RAAS and found significant haplotype-phenotype interaction. Functional studies to confirm or refute these findings are warranted.

Correlation of angiotensin-converting enzyme 2 gene polymorphisms with stage 2 hypertension in Han Chinese.

Experimental evidence indicates that angiotensin-converting enzyme 2 (ACE2), a homologue of human ACE, might negatively regulate the activated renin-angiotensin-aldosterone system (RAAS) and might function as a protective regulator in the pathogenesis of hypertension. However, association studies regarding ACE2 are sparse in the literature, with negative results in the majority of cases. Here we conducted an association study between 2 intronic polymorphisms (A1075G and G8790A) of the ACE2 gene and stage 2 hypertension in Han Chinese. We genotyped the 2 polymorphisms in 1494 subjects (808 stage 2 hypertensives and 686 normotensives) recruited from the Fangshan district (Beijing). Data were analyzed using chi(2) test, 1-way analysis of variance, and logistic regression where appropriate. The frequency of A1075G allele distribution in males differed significantly (P < 0.0001), whereas the genotype and allele distributions of G8790A polymorphism were similar, between stage 2 hypertensives and normotensives. Systolic blood pressure (SBP) differed significantly in females across both genotypes: SBP was significantly lower in subjects with the 1075AA and 8790GG genotypes, higher in the 1075GG (+13.65 mm Hg versus AA) and 8790AA (+13.36 mm Hg versus GG) genotypes, and intermediate in the 1075AG (+5.76 mm Hg versus AA) and 8790GA (+5.65 mm Hg versus GG) genotypes. Our data suggest that the polymorphism (A1075G) might be a risk factor-at least a marker-for stage 2 hypertension in males and that the 2 studied polymorphisms might be the indicators of systolic hypertension in females.

[A1166C polymorphism of the angiotensin II type 1 receptor gene and essential hypertension in Han, Tibetan and Yi populations].

OBJECTIVE: To clarify whether A1166C polymorphism of the angiotensin II type 1 receptor (AT(1)R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China. METHODS: This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in genomic DNA. The data were analyzed by ANCOVA, chi-square test, and multiple logistic regression. RESULTS: In normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (chi-square=4.166, P=0.125). The frequency of the A1166 allele in Tibetan male hypertensives was significantly higher than that in normotensives (chi-square=11.46, P=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (P=0.465) or Yi (P=0.357) populations. Body mass index in the Han and Yi populations (P=0.0001), age in the Tibetan and Yi populations (P=0.0001), and AA genotype in the Tibetan male population (P=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (P=0.0040). CONCLUSION: The A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT(1)R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT(1)R gene is probably not involved in the pathogenesis of essential hypertension in Han and Yi populations.

A1166C polymorphism of the angiotensin II type 1 receptor gene and essential hypertension in Han, Tibetan and Yi populations.

Our aim was to clarify whether substitution of cytosine for adenine at position 1166 (A1166C) polymorphism of the angiotensin II type 1 receptor (AT1R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China. This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymelase chain reaction of genomic DNA and restriction fragment length polymorphism (PCR-RFLP) in genomic DNA. The data were analyzed by analysis of covariance (ANCOVA), X2 test, and multiple logistic regression. In normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (X2=4.166, p=0.125). The frequency of the A1166 allele was significantly higher in Tibetan male hypertensives than that in normotensives (X2=11.46, p=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (p=0.465) or Yi (p=0.357) populations. Body mass index in the Han and Yi populations (p=0.0001), age in the Tibetan and Yi populations (p=0.0001), and AA genotype in the Tibetan male population (p=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (p=0.0040). We concluded that the A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT1R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT1R gene is probably not involved in the pathogenesis of essential hypertension in Han or Yi populations.