Association Of GRK4 Gene Polymorphism With Hypertension And Salt Sensitivity Of Blood Pressure Among Tibetan Population In Gannan Tibetan Autonomous Prefecture

Objective:To investigate the association of G protein-coupled receptor kinase 4(GRK4)gene polymorphism with hypertension and salt sensitivity of blood pressure among Tibetan population in Gannan Tibetan Autonomous Prefecture.Methods:A total of 1,447 Tibetan adults,including 787 Tibetans with essential hypertension and 660 Tibetans with normal blood pressure,were selected in the Tibetan region of Gannan with multistage random sampling method from June 2013to November 2014.Uniform questionnaire was used to survey.Height,and weight,and blood pressure were examined.The salt sensitivity was confirmed by the improved acute salt load test method in China.The DNA was extracted from peripheral venous blood(6 mL),and detected the genotypes of the single nucleotide polymorphisms(SNP)loci in GRK4 genes by Sequenom MassARRAY.The differences of distribution of genotypes and alleles at each locus among hypertension group and normal blood pressure group were analyzed by?~2-test.Binary-Logistic regression was used to analyze the role of GRK4 on hypertension.According to blood pressure and salt sensitivity test results,the subjects were divided into four groups including salt-sensitive hypertension,non-salt-sensitive hypertension,salt-sensitive non-hypertension and non-salt-sensitive non-hypertension.The differences of genotypes distribution and alleles at each locus among different groups were analyzed by?~2-test.Binary-Logistic regression was used to analyze the relationship between GRK4 gene and salt sensitivity in hypertension group and normal blood pressure group.Multivariate-Logistic regression was used to analyze the relationship between GRK4 gene and salt sensitive hypertension in Tibetan population.Result:1.Comparison of basic features:A total of 1,447 participants,including 787 in the hypertension group(554 salt sensitive subjects and 233 salt insensitive subjects),and 660 in the normal hypertension group(423 salt sensitive subjects and 237 salt insensitive subjects).The salt sensitivity,age,gender,body mass index(BMI),education level,smoking,drinking and physical exercise all were significantly different between hypertension group and normal blood pressure group(all P<0.05).2.Genotyping and Hardy-Weinberg's genetic balance:Six SNPs(rs2488815,rs12506119,rs1419043,rs1801058,rs2471338 and rs3733219)were successfully detected in GRK4 gene.Three genotypes of CT,CC and TT were detected at rs2488815.Three genotypes of GG,GA and AA were detected at rs12506119.Three genotypes of CG,CC and GG were detected at rs1419043.Three genotypes of CT,CC and TT were detected at rs1801058.Three genotypes of CA,CC and AA were detected at rs2471338.Three genotypes of CT,CC and TT were detected at rs3733219.The four SNPs of rs12506119,rs1419043,rs2471338 and rs3733219 in GRK4 gene were consistent with Hardy-Weinberg's genetic balance in both hypertension group and normal blood pressure group(all P>0.05).3.Effects of GRK4 gene polymorphism and salt sensitivity and their interactions on hypertension:The distribution of genotypes and allele frequencies in rs12506119 and rs1419043 were significantly different between hypertension group and normal blood pressure group(all P<0.05).The distribution of genotypes and allele frequencies in rs2471338 and rs3733219 were no significantly different between hypertension group and normal blood pressure group(all P>0.05).After adjusting for age,BMI,gender,education,occupation,smoking,drinking and physical exercise,the Binary-Logistic regression analysis showed that the genotype carrying C allele(CG+CC genotype)was a protective factor for hypertension,compared with GG genotype at rs1419043(OR=0.13,95%CI=0.05~0.35,P<0.01).The interaction between rs1419043 gene polymorphism and salt sensitivity leads to an increased risk of hypertension(OR=4.07,95%CI=1.24~13.33,P=0.02).4.Relationship between GRK4 gene polymorphism and salt sensitivity of blood pressure4.1 Hypertension group:The distribution of allele frequencies in rs1419043 was significantly different between salt-sensitive hypertension group and non-salt-sensitive hypertension group(P<0.05).The distribution of genotypes and allele frequencies in other SNPs were no significantly different between salt-sensitive hypertension group and non-salt-sensitive hypertension group(all P>0.05).After adjusting for confounding factors(age,BMI,gender,education,occupation,smoking,drinking and physical exercise),the Binary-Logistic regression analysis showed that GRK4 gene was not associated with salt sensitivity in hypertension group(all P>0.05).4.2 Normal blood pressure group:The distribution of genotypes and allele frequencies in GRK4 gene were no significantly different between salt-sensitive non-hypertension group and non-salt-sensitive non-hypertension group(all P>0.05).After adjusting for confounding factors(age,BMI,gender,education,occupation,smoking,drinking and physical exercise),the Binary-Logistic regression analysis showed that GRK4 gene was not associated with salt sensitivity in normal blood pressure group(all P>0.05).5.Relationship between GRK4 gene polymorphism and salt sensitivity hypertension in four groupsThe distribution of genotypes and allele frequencies in rs12506119 and rs1419043 were significantly different among four groups(all P<0.05).The distribution of genotypes and allele frequencies in rs2471338 and rs3733219 were no significantly different among four groups(all P>0.05).Non-salt-sensitive non-hypertension was used as control,after adjusting for confounding factors(age,BMI,gender,education,occupation,smoking,drinking and physical exercise),Multivariate-Logistic regression analysis showed that the genotype carrying C allele(CG+CC genotype)was a protective factor for salt-sensitive hypertension group compared with GG genotype at rs1419043(OR=0.45,95%CI=0.24~0.84,P=0.01).Conclusion:1.This study found that GRK4 gene locus rs1419043 may be associated with the occurrence of hypertension among the Tibetan population in Gannan.There was an interaction between rs1419043 and salt sensitivity.2.This study found that GRK4 gene locus rs1419043 may be associated with the occurrence of salt-sensitive hypertension in the Tibetan population.