高血压病合并心房颤动患者ACE多态性与TGFβ_1/CTGF的关系

Correlation between angiotensin converting enzyme gene polymorphisms and TGFβ_1/CTGF in hypertensive patients with atrial fibrillation

目的探讨高血压病(EH)合并心房颤动(AF)患者血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与转化生长因子β1(TGFβ1)、结缔组织生长因子(CTGF)的关系。方法选择75例EH合并AF患者分为阵发性AF组(EH+p AF,44例)和慢性AF组(EH+c AF,31例),记录一般临床资料及行超声心动图检查,用ELISA法测定血清TGFβ1、CTGF,用PCR方法检测ACE基因插入/缺失(I/D)多态性,并与EH且为窦性心律(SR)组(EH+SR,37例)及健康对照者(NC,36例)进行比较;比较EH+AF组不同基因型间TGFβ1与CTGF的血清浓度。结果 EH+c AF组和EH+p AF组血清TGFβ1及CTGF水平均显著高于EH+SR组和NC组(P<0.01);EH+AF组与EH+SR组、NC组ACE I/D多态性缺失纯合型(DD型)、杂合子(DI型)、插入纯合型(II型)基因型频率比较差异均无统计学意义(P>0.05),但D等位基因分布频率在EH+AF组中较EH+SR组和NC组明显增加(P<0.05);EH+AF组不同基因型之间TGFβ1及CTGF浓度比较发现,DD基因型TGFβ1浓度显著高于DI型(P<0.01)和II型(P<0.01),DD基因型CTGF浓度明显高于II型(P<0.05)。结论 D等位基因可能是高血压病合并心房颤动的易患基因;房颤患者ACE DD基因型TGFβ1和CTGF水平明显升高,藉此可引起心房肌纤维化及心房重构,导致房颤的发生和发展。

Objective To explore the relationship between the polymorphisms of angiotensin converting en-zyme （ACE） insertion/deletion （I/D） gene and transforming growth factorβ1 （TGFβ1）/connective tissue growth factor （CTGF） in patients with essential hypertension （EH） and atrial fibrillation （AF）. Methods Seventy-five EH patients with documented AF were divided into the paroxysmal AF group （EH＋pAF group, n=44） or the chronic AF group （EH＋cAF group, n=31）, and 37 EH patients with sinus rhythm （SR） were selected into the EH＋SR group. All clinical data including blood pressure, lipids, glucose and atrial diameter measured from ultrasonic cardiogram were recorded. Thirty-six healthy subjects from the medical examination center were assigned to normal controls （NC group）. The se-rum TGFβ1, CTGF were measured by ELISA method, and the genotypes of ACE （I/D） gene were identified by poly-merase chain reaction （PCR） and PCR restricted fragment length polymorphism assay. TGF β1/CTGF concentration and ACE I/D genotypes were compared within different groups. Results The serum TGFβ1 and CTGF levels of EH＋pAF and EH＋cAF groups were significantly higher than those of EH＋SR and NC group （P〈0.001, respectively）. In spite of no difference of ACE I/D genotypes between the four groups, allele D genotype frequency in EH＋AF group was significantly higher than that in EH＋SR and NC groups （P〈0.05）. Among the patients in EH＋AF group, the serum TGFβ1 concentration was significantly higher in patients with DD genotype than in those with ID andⅡgenotypes （P〈0.05 and P〈0.01, respectively）, and the serum CTGF level was also markedly higher in patients with DD genotype than in those with ID andⅡgenotypes （P〈0.05）. Conclusion The allele D may be the risk factor for AF in EH pa-tients. The serum TGFβ1/CTGF levels were markedly elevated in AF patients with DD genotype of ACE, which may cause atrial fibrosis and atrial remodeling, resulting in the occurrence and development of atrial fibrillation.