Relationship Between C6749T Polymorphism In WNK4 Gene And Essential Hypertension In Xinjiang Kazaks Population

BackgroundWNK4 gene(with no K=lysine kinase)is a newly cloned protein kinase gene.It is a small group of serine/threonine kinase with unique catalytic domains that lack the lysine residue used in other kinases to co-ordinate ATP,hence,with No K[WNK]. Mutations in extron 7and 17 have been shown to cause the rare autosomal dominant disorder pseudohypoaldosteronism typeⅡ(PHAⅡ),which is characterized by hypertension,hyperpotassemia and metabolic acidosis.Otherwise,WNK4 gene locates in human chromosome 17 which harbors genes that influence blood pressure. So maybe there is a close relationship between the mutations of WNK4 gene and essential hypertension.Erlich PM Group attempted to investigate the relationship between the genetic variants of WNK4 and hypertension.But there was no significant difference between extron7 C6749T polymorphism and their hypertension in African Americans and white Americans.But there is a report.They found that there was a relationship between extron7 C6749T(rs9916754)polymorphism and their hypertension.All subjects(98 hypertensives and 95 normotensives)came from Zhangwu County of Liaoning province where there is a high incidence of hypertension.Why are two findings different? Maybe there is an ethnic and territorial specificity with regard to gene sensitivity of hypertension.So,we should targeted people in different territory and ethnic as research objects.The prevalence of hypertension in Xinjiang Kazaks population ranked the fifth among whole country.So we choose Kazaks population as subjects to approach the relationship between C6749T of WNK4 gene and essential hypertension.ObjectiveA population based case-control study was set up to explore the association between C6749T polymorphism of WNK4 gene and essential hypertension in Xinjiang Kazaks population.Besides,we aim to assess the interaction effect between WNK4 gene C6749T mutation and environment factors on EH.MethodsResearch workers collected Kazak samples when they carry out epidemiological survey about hypertension in Xinjiang autonomous region of China.To reject samples which lack some index,there are 897 samples totally(age≥30 years).The cases all accord to WHO diagnostic criteria:SBP≥140 and(or)DBP≥90.The controls contain subjects whose SBP≤140 and DBP≤90.If somebody eated ills in last two weeks or were ever diagnosised as hypertension,he belongs to case group.By Taqman probe technique,we genotyped C6749T polymorphism of WNK4 gene in 556 hypertensives and 341 normotensives,aiming to reveal the genotypes frequency and alleles frequency between case group and control group.Besides,by unconditional logistic regression model,we analyzed the roles of gene polymorphism and environmental factors about hypertension.Addictive model was applied to assess the interaction effect between WNK4 gene C6749T mutation and environment factors on EH.Results1.The distribution of genotype and allele of C6749T(rs9916754)site in Xinjiang Kazaks populationIn 897 objects,there are three genotypes,the frequency of CC genotype is 94.9%, the frequency of CT genotype is 5.0%,and the frequency of TT genotype is 0.1%.The frequency of allele C is 97.4,and allele T is 2.6%.2.Comparison of frequencies of genotypes and alleles between case and control groupsThe frequency of WNK4 C6749T genotypes in the case and control group were CC:93.2%verse 97.7%,CT:6.6%verse 2.3%,TT:0.2%verse 0.0%.Allele frequencies were C:93.3%verse 97.7%,T:6.7%verse 2.3%.There was a significant difference between CC group and CT+TT group(x~2=8.87,P=0.003).There was also a significant difference in allele frequency distribution between case and control group (x~2=9.15,P=0.0025).3.Unconditional logistic regression(1)By unconditional logistic regression model,it showed age,BMI,TC and WNK4 gene C6749T mutation were risk factors for the essential hypertension.(2)So after adjusted for age,gender,BMI,TC,TG,GLU by using unconditional logistic regression model,there was still a significant relationship between hypertension and C6749T polymorphism of WNK4 gene.The odds ratio for hypertension of allele T verse allele C is 3.57(x~2=9.69,P=0.002,OR=3.57, 95%CI=1.60-7.90)(compared with TT genotype).(3)By analysis of covariance,there was a relationship between WNK4 gene C6749T mutation and SBP in men;while there was also a relationship between WNK4 gene C6749T mutation and SBP and DBP in women.4.Interaction between WNK4 gene C6749T mutation and environment factors: The result of interaction between C6749T mutation and environment factors were as following:There was a positive interaction between WNK4 gene C6749T mutation and gender,BMI,GLU.(1)There was a positive interaction between WNK4 gene C6749T mutation and gender after adjusted for age,BMI,GLU,TG,TC by logistic analysis,and the OR was 3.85(95CI:1.23～12.04).This indicated that the concurrence of C6749T mutation and female may have the higher risk of EH.(2)There was a positive interaction between WNK4 gene C6749T mutation and BMI after adjusted for age,gender,GLU,TG and TC by logistic analysis,and the OR was 5.91(95CI:1.99～17.57).(3)There was a positive interaction between WNK4 gene C6749T mutation and GLU after adjusted for age,gender,BMI,TG and TC by logistic analysis,and the OR was 8.77(95CI:1.04～73.93). Conclusions1.There is a relationship between C6749T polymorphism of WNK4 gene and the essential hypertension in the Xinjiang Kazaks population.T allele maybe a risk factor to the essential hypertension.2.The interaction analysis between WNK4 gene polymorphism and environment factors were first explored in this study.The results showed that there were interactive effects between WNK4 gene C6749T mutation and gneder,BMI,GLU.