| Objective: This study aimed to explore the association between PCSK6 and Corin genes and the genetic susceptibility to hypertension in the Chinese Han population.Methods: This study conducted a baseline survey of the two communities(Guanlin and Xushe)in Yixing City,Jiangsu Province,China on May 10,2009 through a cluster sampling method.A total of 4128 people were investigated,including 2012 cases of hypertension and 2116 cases.For normal blood pressure controls,another 94 normal elderly controls were added.At the same time,2116 normal blood pressure controls were followed up to obtain the outcome of their hypertension.Four loci of PCSK6 gene(rs1030,rs1135911,rs2949,rs1871977)and four loci of Corin gene(rs11934749,rs2289433,rs3749585,rs4695253)were selected for association study.Logistic regression model was used to analyze the association between PCSK6 and Corin gene variants and hypertension in case-control studies of hypertension by calculating Odds ratio(OR)and 95% Confidence interval(CI).The association of PCSK6 and Corin gene variants with hypertension risk in follow-up studies was analyzed using Cox proportional risk regression model by calculating Hazard ratio(HR)and 95%CI.The General linear model(GLM)was utilized to analyze the differences of quantitative traits of blood pressure among different genotypes.Unconditional logistic regression model and the Cox proportional hazard regression model were used to analyze the gene-environment interaction effect under the condition of dominant genetic model.Results: A case-control study of hypertension showed that PCSK6 and Corin genes were not found to be significantly associated with hypertension in the general population.However,the results of subgroup analysis showed that in the group ≥55 years old,the PCSK6 gene rs1030(C>T)locus mutation was associated with an increased risk of hypertension.After adjusting the covariance,the OR value(95%CI)of the additive model was 1.169(1.026~1.333)(P=0.019);the OR value(95%CI)of the dominant model was 1.245(1.061~1.461)(P=0.007).The results of gene-environment interaction analysis showed that there was an interaction between PCSK6 gene rs1030 locus variation and age ≥55 years old.After adjusting the covariance,the OR(95%CI)was 1.355(1.018~1.802)(P=0.037).Follow-up studies showed that in the total population,the PCSK6 gene rs2949 locus C>T mutation increased the risk of hypertension,and the incidence density of CC,CT,and TT genotypes were 6.37,6.94,and 7.90(/100 person-years),respectively.The HR(95%CI)of the additive model was 1.139(1.018-1.276)(P=0.024).The Corin gene rs11934749 locus C>T variant reduced the risk of hypertension.The HR(95%CI)of the additive model was 0.602(0.424~0.855)(P=0.005),after adjustment of related covariates.The HR of recessive model(95%CI)was 0.635(0.434~0.929)(P=0.019).Subgroup analysis showed that PCSK6 rs2949 C>T locus variation increased the risk of hypertension in the group ≥55 years,and its additive model HR=1.178(1.032~1.344)(P=0.015);recessive model HR=1.261(1.038~1.531)(P=0.019).Corin gene rs11934749 C>T locus mutation reduces the risk of hypertension,its additive model HR=0.577(0.358~0.930)(P=0.024);recessive model HR=0.590(0.356~0.977)(P=0.040).In the group < 55 years,the variation of Corin rs2289433 T>C locus was associated with a reduced risk of hypertension HR(95%CI))of 0.749(0.589~0.952)(P=0.018);0.737(0.545~0.996)(P=0.047),respectively.In the male population,Corin rs11934749 C>T locus vary significantly reduced the risk of hypertension.After adjusting the correlation covariance,the additive model HR=0.487(0.275-0.861)(P=0.013);recessive model HR=0.512(0.271-0.967)(P=0.039).Corin rs4695253 C>T locus vary significantly increased the risk of hypertension,HR(95%CI)was1.344(1.036-1.744)(P=0.026);1.371(1.035~1.816)(P=0.028),respectively.Among non-smokers,the Corin rs1193474 C>T locus vary significantly reduced the risk of hypertension HR(95%CI)of 0.560(0.371~0.845)(P=0.006);0.585(0.371~0.921)(P=0.021),respectively.In the non-drinking population,the HR(95%CI)of the Corin rs11934749 C>T point additive model was 0.620(0.415~0.928)(P=0.020),indicating that rs11934749 locus variation was significantly correlated with the risk reduction of hypertension.The results of quantitative analysis of blood pressure showed that the differences in the systolic and diastolic blood pressure levels of the different genotypes(AA,AC,CC)at rs1871977 of the PCSK6 gene in the non-medicated group were statistically significant.The systolic blood pressures were(143.55±11.16)mm Hg,(142.71±11.60)mm Hg and(138.11±13.96)mm Hg,P=0.007;diastolic blood pressure were(87.86±7.86)mm Hg,(87.53±7.48)mm Hg and(84.37±8.63)mm Hg,P=0.009.In addition,the systolic blood pressure levels(124.49±11.14)mm Hg,(123.82±11.75)mm Hg and(118.65±14.78)mm Hg of the different genotypes(CC,CT,TT)at the rs4695253 locus of the Corin gene in the control group were statistically significant(P<0.05).Conclusion: 1.This study was based on a case-control study and prospective cohort study in Chinese Han population to explore the association between PCSK6 and Corin genes and hypertension.The results suggested that PCSK6 gene and Corin gene genetic variation may be associated with hypertension in Chinese Han population.2.Age might change the genetic effect of PCSK6 gene on hypertension by modifying gene expression.Age,sex might change the genetic effect of Corin gene on hypertension by modifying gene expression.3.The combination of PCSK6 rs1871977 locus and Corin rs4695253 locus variation and antihypertensive drugs has a certain influence on the blood pressure level of the population. |
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