Association Of Polymorphism Of The Endothelial Nitric Oxide Synthase Gene With Essential Hypertension In Han,Miao And Bouyei Ethnicities In The Guizhou Province Of China

Objective: To investigate the association of polymorphism of three SNP loci,i.e.the rs2070744 in the promoter region,the rs1799983 in exon 7 and the rs3918181 in intron 14,and one VNTR locus(intron 4 th a variable number of a tandem repeat of a 27-bp sequence in intron 4)in the human eNOS gene with essential hypertension(EH)in the Han,Miao and Bouyei ethnic habitants in the Guizhou province of China.Methods: A cohort of 456 participants with primary hypertension(195 cases of Han ethnicity,127 cases of Miao ethnicity and 134 cases of Bouyei ethnicity)as well as 453 cases of healthy participants included as normal controls(206 cases of Han ethnicity,111 cases of Miao ethnicity and 136 cases of Bouyei ethnicity)were recruited in this study.All hypertension patients are in line with the 2010 Chinese guidelines for prevention and treatment of hypertension standards.Clinical data were collected,including participants' height and weight.The levels of total cholesterol(TC),triglyceride(TG),fasting blood glucose and uric acid(UA)were tested and recorded.The eNOS gene in the rs2070744,rs1799983 and rs3918181 loci were determined using TaqMan probe technique.The polymorphism of the 27-bp VNTR was detected using PCR and agarose gel electrophoresis and all the loci were identified with DNA sequencing.The relationship between each genotype and EH was analyzed.Risk factors of EH were measured using a Logistic regression analysis,with a p<0.05 set for statistical significance.Results:(1)Polymorphism distribution of the rs1799983,rs2070744,rs3918181 and 27 bp VNTR of the eNOS gene in the EH and control groups of the three ethnic groups were consistent with the Hardy-Weinberg equilibrium.(2)Compared with the controlgroups,the age and body mass index(BMI)as well as the fasting plasma glucose,TC and TG levels of the EH group in the Han group were significantly different.According to the national stratification,the age and BMI as well as the fasting blood glucose,TC and TG levels of the EH group in the Han and Bouyei groups were higher than those of the normal counterparts.The age and BMI as well as the fasting blood glucose levels of the EH group in the Miao group were higher than those in the corresponding normal controls,with statistically significant differences between the two groups.Logistic regression analysis showed that the age and the fasting blood glucose level may be independent risk factors for the EH in the Han ethnicity.The age and BMI as well as the fasting blood glucose lvel may be independent risk factors for the EH in the Miao and Bouyei ethnicities.(3)Compared with the corresponding normal controls,the genotype distribution frequency and the allele distribution frequency of the rs2070744,rs3918181 and 27 bp VNTR of the eNOS gene in the EH group were not statistically significant(P>0.05).According to the national stratification,the genotype distribution frequency and the allele distribution frequency of the rs2070744,rs3918181 and 27 bp VNTR of the eNOS gene in the EH group of the three ethnicities were not statistically significant(P>0.05).(4)Compared with the Bouyei group,there was a significant difference in the genotype frequency and the allele frequency of the rs1799983 locus in Han and Miao groups(P<0.05).There was a statistical significance in the genotype frequency and the allele frequency of the27-bp VNTR locus between the Han and Miao ethnicities(P < 0.05).Compared with the Han,there was no significant difference in the genotype frequency and the allele frequency of the rs2070744 and rs3918181 loci between the Miao and Bouyei(P>0.05).(5)There was a strong linkage disequilibrium between the rs2070744 and the27-bp VNTR.(6)Haploview 4.1 software was used to construct and analyze the haplotype of the rs2070744,27-bp VNTR,rs1799983 and rs3918181 loci.The haplotype T-b-G-G and T-b-G-A were higher than the others,there was no significant difference in the haplotype combination between the EH and the control groups.Conclusion:(1)The polymorphism at the rs2070744,rs1799983,rs3918181 and27 bp VNTR loci of the eNOS gene may not be related to the occurrence of EH in theGuizhou Han,Miao and Bouyei ethnic habitants.The haplotypes constructed at the four loci may not be related to the EH in Guizhou.(2)There was a significant difference in the genotype distribution frequency and the allele distribution frequency of the rs1799983 and 27-bp VNTR loci in the Guizhou Han,Miao and Bouyei ethnic habitants.However,there was no significant difference in the genotype distribution frequency and the allele distribution frequency of the rs2070744 and rs3918181 loci in the Han,Miao and Bouyei ethnicities.(3)The age and BMI as well as the fasting blood glucose,TC and TG levels may be predisposing factors for the EH in the Guizhou habitants.Logistic regression analysis shows that age and BMI as well as the fasting blood glucose levels may be independent risk factors for EH in Guizhou habitants.(4)There was a strong linkage disequilibrium between the rs2070744 and27-bp VNTR loci in Guizhou habitants.