002, resp.). Nevertheless, this difference was not observed between male inhibitor Pacritinib patients and male controls (Table 3). After adjusting confounding factors (such as gender, age, smoking, drinking, hypertension, diabetes, blood lipid, and blood glucose), the AG genotype frequency and A allele frequency were still associated with IS, and both were protective factors (OR = 0.572, 95% CI: 0.335�C0.978, P = 0.041, and OR = 0.611, 95% CI: 0.378�C0.985, P = 0.041, resp.) (Table 2). Similar finding was also observed in female patients in stratification analysis (OR = 0.328, 95% CI: 0.153�C0.703, P = 0.004, and OR = 0.347, 95% CI: 0.174�C0.691, P = 0.002, resp.) (Table 4).Table 2Genotype and allele frequency of 4 sites of NOS1 gene��.Table 3Genotype and allele frequency in males and females.
Table 4Regression analysis in females��.The online SHEsis software was employed to test the pair linkage disequilibrium of 4 sites. Results showed linkage disequilibrium in rs2139733 and rs2293050 (P1 = 0.995, P2 = 0.977). The frequency of potential haplotypes composed of 4 sites (rs1483757, rs2139733, rs2293050, and rs7308402) was also evaluated in patients and controls with SHEsis. Results showed that GATA haplotype frequency in IS patients was dramatically lower than that in controls, suggesting that GATA haplotype is a protective haplotype (OR = 0.593, 95% CI: 0.361�C0.977, P = 0.038) (Table 5).Table 5Haplotype frequency of NOS1 gene in patients and controls.4. DiscussionIn the present study, 4 SNP sites (rs1483757, rs2139733, rs2293050, and rs7308402) of NOS1 gene were detected in Han Chinese with IS of North China, and their relation with IS was evaluated in this population.
Our results showed that the genotypes and allele frequency of rs1483757, rs2139733, and rs2293050 were comparable between IS patients and control, but the AG genotype and A allele frequency of rs7308402 were markedly reduced in IS patients when compared with healthy controls (P = 0.037, P = 0.041). After adjusting traditional confounding factors (gender, age, hypertension, diabetes, smoking, drinking, and blood lipid), the AG genotype and A allele frequency of rs7308402 were still related to IS (OR = 0.572, 95% CI: 0.335�C0.978, P = 0.041 and OR = 0.61, 95% CI: 0.378�C0.985, P = 0.041, resp.). These findings suggest that SNP of rs7308402 may be a genetic marker of female Han patients with IS in North China.
Yamaguchi et al. [24] and our previous studies [25, 26] also revealed the difference in some SNPs related to IS between males and females, which was also confirmed in this study. The cause of this difference is still unclear and the difference in sex hormone might be an attributor. Lekontseva et al. [27] investigated Drug_discovery the resistant vessels in female animals. Their results showed nNOS mediated dilation of arteries in vitro.Haplotype analysis may overcome the disadvantage of little information provided by SNP analysis. Haplotype has low recombination rate and high stability.
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