| Objective: Essential hypertension is a chronic noncommunicable disease with complicated pathogenesis and numerous risk factors.At present,several studies have shown that the Gab1,Gab2 and Gab3 genes in the Gab family protein may be involved in the development of hypertension by regulating the signaling pathway.The purpose of this study was to analyze the association between gab1/2/3 gene polymorphism and essential hypertension from the perspective of genetic susceptibility,so as to provide etiological clues for the pathogenesis of hypertension and provide new targets for disease prevention and treatment.Methods: The method of cluster sampling was used to study the epidemiology of rural population in two towns in yixing city,jiangsu province.A total of 4222 subjects were included,including 2012 in the hypertension group and 2210 in the healthy control group.Baseline data were collected and the healthy control group was followed up for an average of 5.01 years.Finally,seven sites of rs300893 and rs11936966 of Gab1 gene,rs2450135,rs7107174 and rs3740677 of Gab2 gene,and rs3813455 and rs5987015 of Gab3 gene were selected for genotyping using Taqman probe technology.The associations of polymorphisms of different genotypes and the incidence of hypertension were analyzed using a binary logistic regression model,and the follow-up data were analyzed using Cox risk regression analysis.Stratified analysis was conducted according to age,gender,smoking and drinking,and the additive/dominant/recessive models were analyzed respectively.A general linear model was used to compare blood pressure levels between groups.Results: Logistic regression results show that after adjusting for related covariates inthe general population,except for the rs7107174 C> T mutation at the Gab2 gene locus(CC + CT vs.TT,OR = 1.204,95% CI = 1.019-1.423,P = 0.029)and In addition to the risk of hypertension,other SNPs were not significantly associated with hypertension susceptibility(P> 0.05).The results of stratified analysis showed that the rs5987015 A> G mutation on Gab3 in the subgroup <55 years of age(AA vs.AG vs.GG,OR = 1.220,95% CI = 1.028-1.448,P = 0.023)was significantly associated with an increased risk of hypertension;in the group ? 55 years old,the locus on Gab1 was rs300893 T > C(TT vs.TC + CC,OR = 1.182,95% CI = 1.013-1.380,P= 0.033)was associated with the risk of hypertension.In the female subgroup,the Gab1 epitope was rs300893 T > C(TT vs.TC vs.CC,OR = 1.155,95% CI =1.007-1.325,P = 0.039)indicated that the site variation is associated with the onset of hypertension.In the non-smoker group,the Gab1 epitope was rs300893 T > C(TT vs.TC vs.CC,OR = 1.133,95% CI = 1.004-1.279,P = 0.042)and rs7107174 C >T(CC + CT vs.TT,OR = 1.284,95% CI = 1.059-1.556,P = 0.011)at Gab2 both indicated site mutations It is associated with an increased risk of hypertension.In the drinking group,rs7107174 C > T(CC vs.CT vs.TT,OR = 1.228,95% CI =1.006-1.499,P = 0.044)at the Gab2 epitope suggests that site variation will increase the risk of hypertension,and the difference has Statistical significance.A follow-up study of the control population found that in the <55-year-old stratification,the rs7107174(C> T)mutation in the Gab2 gene can reduce the risk of hypertension,and its additive model(CC vs.CT vs.TT),HR = 0.797(0.642-0.989),P = 0.039,and rs7107174 implicit model(CC + CT vs.TT),HR = 0.488(0.302-0.789),P = 0.003 and rs2450135 explicit model(GG vs GA + AA),HR = 1.462(1.085-1.972),and P =0.013 all indicate that the site mutation is significantly associated with the onset of hypertension.In stratification ?55 years of age,the rs3813455(C> G)mutation in the Gab3 gene can also reduce the risk of hypertension,with HR = 0.691(0.512-0.932)and P = 0.015.In the gender grouping,both male and female stratification suggested that the rs7107174(C> T)mutation in the Gab2 gene had a statistically significant difference in the risk of hypertension(P <0.05),and the additive model HR = 1.210(1.011-1.447)(P = 0.038),recessive model HR = 1.419(1.047-1.924)(P = 0.024);additive model HR = 0.828(0.712-0.964)(P = 0.015)in female group,recessive model HR = 0.645(0.476-0.874)(P = 0.005).The results of studies on the effect of gene polymorphisms on blood pressure levels in the treated and untreated groups showed that after adjusting for related variables,the diastolic blood pressure level of wild type carriers(CC)at the rs3813455 position on the Gab3 gene in the untreated group(81.82±7.91)mmHg,heterozygous(CG)(81.16±8.40)mmHg and mutant(GG)(81.35±8.10)mmHg are statistically different(P=0.015);its wild type(130.23±14.29)mmHg,There was also a statistically significant difference in systolic blood pressure between the heterozygous(127.55 ± 14.76)mmHg and mutant(128.86±13.56)mmHg(P=0.027).The systolic blood pressure level(130.45 ± 14.40 and127.94±13.93)mmHg in the rs5987015 locus of the Gab3 gene and the GG gene carrier(130.55±14.15)mmHg are different(P=0.001);and rs5987015 locus There was also a statistically significant difference in the diastolic blood pressure levels of type 82 carriers(82.45±7.83),(80.34±8.06),(81.92±7.91)mmHg(P<0.001).Conclusion: The TT genotype at rs7107174 on the Gab2 gene may be a risk factor for hypertension in Chinese han population.Rs300893 on Gab1 was a risk factor for hypertension in people aged ?55 years and women,and rs5987015 on Gab3 was a risk factor for hypertension in people aged < 55 years.Rs300893 on Gab1 was found to be a risk factor of hypertension in people with no smoking behavior,while rs2450135 on Gab2 was found to be a risk factor of hypertension in people with drinking behavior and rs7107174 on people with no smoking or drinking behavior.The interaction between rs3813455 and rs5987015 mutation genes on Gab3 and antihypertensive drug treatment has a certain effect on the blood pressure level of the population... |
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