Aucella F, Vigilante M, Margaglione M, Grandone E, del Popolo A, Forcella M, Procaccini D, Salatino G, Passione A, Ktena M, De Min A, Stallone C
Department of Nephrology and Dialysis, Casa Sollievo della Sofferenza, Hospital IRCCS, San Giovanni Rotondo, Italy.
Nephron. 2000 May;85(1):54-9. doi: 10.1159/000045630.
The plasma levels of angiotensin-converting enzyme (ACE) are modulated by the insertion (I)/deletion (D) polymorphism within the ACE gene locus. An association between progressive renal disease, raised cardiovascular risk, and ACE plasma levels has been shown. To evaluate the genotype frequencies of the I/D polymorphism in terminal renal failure, we have enrolled 341 dialysis patients (321 on hemodialysis and 20 on peritoneal dialysis) in a district of southern Italy (Foggia). As controls, 1,307 subjects from the same area have been enrolled. Genomic DNA was obtained from leukocytes, and the ACE I/D polymorphism was determined by polymerase chain reaction. Among uremics, 151 subjects (44.3%) carried the DD genotype, 149 (43.7%) the ID, and 41 (12.0%) the II genotype. In controls, 560 subjects (42.8%) had the DD genotype, 577 (44.1%) the ID, and 170 (13.1%) the II genotype (p = n.s.). Among patients, the frequency of DD subjects was higher in men (48.3%) than in women (39. 7%, p < 0.01). A slight different frequency of the DD genotype was found according to the duration of dialysis treatment: 47.5% in patients on dialysis up to 60 months and 41.7 and 40.6% in those with a dialytic age of 60-120 and >120 months, respectively (p for trend: 0.53). Patients with or without cardiovascular diseases, such as hypertension, left ventricular hypertrophy, coronary artery disease, and chronic cardiac failure, did not exhibit any difference in ACE I/D allele and genotype frequencies (p always >0.05). In conclusion, frequencies of the ACE DD genotype were similar in uremics and in controls and did not differ between patients with and without cardiovascular diseases. A nonsignificant inverse relationship with the time spent on dialysis was observed, suggesting that ACE I/D polymorphism may influence the cardiovascular death rate.
血管紧张素转换酶(ACE)的血浆水平受ACE基因座内插入(I)/缺失(D)多态性的调节。已表明进行性肾病、心血管风险增加与ACE血浆水平之间存在关联。为了评估终末期肾衰竭中I/D多态性的基因型频率,我们在意大利南部(福贾)的一个地区招募了341名透析患者(321名接受血液透析,20名接受腹膜透析)。作为对照,招募了来自同一地区的1307名受试者。从白细胞中获取基因组DNA,并通过聚合酶链反应确定ACE I/D多态性。在尿毒症患者中,151名受试者(44.3%)携带DD基因型,149名(43.7%)携带ID基因型,41名(12.0%)携带II基因型。在对照组中,560名受试者(42.8%)具有DD基因型,577名(44.1%)具有ID基因型,170名(13.1%)具有II基因型(p = 无显著差异)。在患者中,男性DD受试者的频率(48.3%)高于女性(39.7%,p < 0.01)。根据透析治疗时间发现DD基因型频率略有不同:透析时间达60个月的患者中为47.5%,透析年龄为60 - 120个月和>120个月的患者中分别为41.7%和40.6%(趋势p值:0.53)。患有或未患有心血管疾病(如高血压、左心室肥厚、冠状动脉疾病和慢性心力衰竭)的患者在ACE I/D等位基因和基因型频率上没有表现出任何差异(p值始终>0.05)。总之,尿毒症患者和对照组中ACE DD基因型的频率相似,患有和未患有心血管疾病的患者之间也没有差异。观察到与透析时间存在无显著意义的负相关关系,提示ACE I/D多态性可能影响心血管死亡率。