摘要
目的：探讨致病基因多态性与狼疮性肾炎（ＬＮ）患者临床表现及预后之间的关系。方法：应用ＰＣＲ方法分别对９８例和１４４例ＬＮ患者的白细胞介素－１受体拮抗剂（ＩＬ－１ｒａ）和血管紧张素转换酶（ＡＣＥ）基因多态性的分布进行观察，并结合临床病理及随访资料进行分析。结果：携带ＩＬ１ＲＮ＊２等位基因的ＬＮ患者光敏感发生率高，ＬＮ活动性病变明显；ＬＮ患者ＡＣＥ基因ＤＤ基因型的发生频率明显高于正常人（Ｐ＜０．０１），ＤＩ型患者肾脏损害较重，预后较差；ＩＬ－１ｒａ和ＡＣＥ基因多态性在ＬＮ患者的分布无明显相关性。结论：ＬＮ的临床多样性可能与致病基因多态性有一定联系。ＬＮ活动者ＩＬ１ＲＮ＊２等位基因携带率较高，ＬＮ患者ＤＤ基因型发生频率较高，ＤＩ型与病情严重性及不良预后相关，但ＩＬ－１ｒａ和ＡＣＥ基因多态性对ＬＮ的影响无协同作用。
Different genetic background may be responsible for the clinical diversity in lupus nephritis (LN). IL 1 receptor antagonist (IL 1ra) inhibit the inflammatory effect of IL 1 by competing for receptor binding. The variable number of tandem repeat (VNTR) polymorphism of IL 1ra gene is associated with the variation of circulatory levels of IL 1ra. Renin angiotensin system is now well established as an important determinant in the progression of renal damage. The deletion/insertion polymorphism of angiotensin converting enzyme (ACE) gene is responsible for the genetic control of serum ACE and has been studied intensively in IgA nephropathy and diabetic nephropathy. The relationship between gene polymorphism and the clinical feature of LN was observed in the present study. METHODOLOGY Polymerase chain reaction assay was applied to analyze IL 1ra gene polymorphisms in 98 LN patients and ACE gene polymorphisms in 144 LN patients. Same number of healthy blood donors were set as controls. RESULTS No significant difference has been found in the distribution of allele frequencies of IL 1ra gene between LN patients and the control. LN patients carrying IL1RN *2 allele showed a higher frequency of photosensitivity ( P <0.05) and active lesions as hematuria ( P <0.01), activation of LN ( P <0.01) and crescent formation ( P <0.05). The distribution pattern of IL1RN *2 allele frequency was not significantly different between patients with stable renal function and those with progressive renal failure. For ACE gene, the DD genotype was significantly more frequent in LN patients than in normal control ( P <0.01), while the II genotype was less frequent in LN patients than in normal control ( P <0.01). It was found that the frequency of DI genotype was significantly higher in patients with type Ⅳ LN, crescent formation and severe tubulo interstitial lesions. Follow up data showed that patients with progressive renal function damage had a higher incidence of DI genotype than those with stable renal function in LN ( P <0.01). There was no relationship in the distribution of gene polymorphism between IL 1ra and ACE gene in patients with LN. CONCLUSION LN patients carrying IL1RN *2 allele tend to have severe active lesions closely related to disease activation. Although IL1RN *2 allele does not predispose to LN, it does serve as a marker to predict disease activation that has been initiated. The DD genotype was significantly more frequent in LN patients than in normal control. In LN patients, the DI genotype, rather than the DD genotype, was associated with disease severity and progression.
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
1997年第1期3-8,共6页
Chinese Journal of Nephrology,Dialysis & Transplantation
基金
军队医药卫生杰出中青年科研基金
关键词
狼疮性肾炎
基因多态性
致病基因
lupus nephritis IL 1 receptor antagonist angiotensin converting enzyme
