Association Between α-adducin Gene,Angiotensin Converting Enzyme Gene Polymorphisms And Hypertensive Kidney Lesions In Hypertensive Patients

Objective : To investigate the association between polymorphisms ofα-adducin(ADD) Gly460Trp and Angiotensin Converting Enzyme (I/D) genes and kidney lesions in patients with essential hypertension respectively and jointly.Methods:The case-control study was performed in 509 hypertensive hospitalized patients and 509 normal subjects(group A) during 2004-2007 according to"China 2004 guideline for the treatment and preservation of essential hypertension". On the basis of creatinine clearance calculated by Cockcroft–Gault equation, hypertensive patients were divided into two groups: normal renal function group(group B:Ccr≥80 ml/min) and abnormal renal function group(group C:Ccr<80 ml/min). Basic clinical data such as sex, age, body mass, height, hierarchy and course of hypertension were collected; Biochemical parameters such as serum creatinine, urea nitrogen, uric acid, fasting plasma glucose, lipids were measured; Polymerase chain reaction (PCR) was used to characterize ACE genotypes (ID, II, DD); PCR and restriction Fragment Length Polymorphism(RFLP) were used to characterizeα-adducin genotypes (GT, GG, TT). Both of them were confirmed by DNA sequencing.The relationship between genes and renal function was analyzed respectively and jointly in patients with essential hypertension.Results: (1) The levels of age, serum creatinine, urea nitrogen and uric acid were higher in group C by comparision with group A and B, and had significant difference (P<0.05) . There was significant difference of serum creatinine between group A and B (P<0.05); While there was no significance of age, urea nitrogen, uric acid between them (P>0.05). There was no significance of sex, body mass index, fasting plasma glucose and lipids among group A, B and C (P>0.05).(2) The expected frequencies of the ACE and ADD genotypes were under the assumption of the Hardy-Weinberg equilibrium in hypertensive group and normal group respectively (P> 0.05).(3) Chi-square test demonstrated that the distributions of ACE DD, ADD TT homozygote and ACE-DD+ADD-TT genetype (23.4%, 26.3% and 8.8% respectively) were higher in group C than group A (the distribution was 10.6%, 14.5% and 1.4% respectively) and group B (the distribution was 11.6%, 15.9% and 1.6% respectively); and had significant difference (P<0.0125).While there was no significance of ACE DD, ADD TT homozygote and ACE-DD+ADD-TT genetype between group A and B (P>0.0125).(4) Binary logistic stepwise regression demonstrated that hypertensive course and ACE-DD +ADD-TT genetype entered the model at last , and was significantly associated with abnormal renal function in group B and C. The odds ratios (OR) were 1.005(95%CI:1.003-1.007)and 4.976(95%CI:1.464-16.913). Conclusion:It was suggested that bothα-adducin TT genotype and ACE DD genotypes were significantly associated with kidney lesions in patients with essential hypertension, respectively or jointly. ACE-DD+ADD-TT genotype can be the independent risk factor of hypertensive kidney lesions.