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Genetic Analysis of Interleukin-10 Promoter Region in Patients with Systemic Lupus Erythematosus in Taiwan

台灣地區全身性紅斑狼瘡病人第十介白質基因啟動區之基因分析

摘要


第十介白質的過度產生可能是全身性紅斑狼瘡或狼瘡腎炎的致病機轉之一,在第十介白質基因啟動區有一多形性雙核苷酸重複區,本實驗主要探討第十介白質基因啟動區對偶質和全身性紅斑狼瘡或狼瘡腎炎之間的關係。 本實驗總共收集100位全身性紅斑狼瘡之病人,其中有49位發展成狼瘡腎炎、以及103位健康正常人為對象,萃取其DNA,然後用PCR及電泳的方法來加以分析。結果發現全身性紅斑狼瘡之病人,在第十介白質基因啟動區對偶質、基因型、及雙核苷酸重複總數和健康正常人組並無差異。就全身性紅斑狼瘡之病人而言,49位有狼瘡腎炎的病人和51位無狼瘡腎炎的病人,在第十介白質基因啟動區對偶質、基因型、及雙核苷酸重複總數,兩組並無差異。但這49位有狼瘡腎炎的病人之中,有10位最後發展成末期腎病,其中有4位其疾病進行過程中是屬於快速進行性腎衰竭,比較這兩組末期腎病的病人,結果發現在快速進行性腎衰竭這組,有較少雙核苷酸重複總數。

關鍵字

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並列摘要


Overproduction of interleukin-10(IL-10) may play an important role in the development of systemic lupus erythematosus (SLE) or lupus nephritis. There is also a polymorphic dinucleotide repeat in the human IL-10 promoter region (IL-10PR). Our aim was to study whether or not the IL-10PR alleles contributed to the susceptibility to SLE or lupus nephritis. One hundred SLE patients and 103 healthy controls were studied for IL-10PR by PCR and electrophoretic analysis. The distribution of IL-10PR alleles, genotypes and the sum of both allelese (SBA) from different groups or subgroups were analyzed. SLE patients showed no difference in the distribution of IL-10PR alleles, genotypes and SBA, as compared to healthy controls. Lupus nephritis patients (N=49) also showed no difference in IL-10PR alleles, genotypes and SBA, as compared to SLE patients without nephritis (N=51). Of 49 lupus nephritis patients, ten developed endstage renal disease (ESRD) and four of them were found to suffer from rapid progressive renal failure (RPRF). Patients with RPRF presented much smaller SBA than other ESRD patients (p=0.005). Lupus nephritis patients carrying small SBA(<18) suffered from a higher prevalence of RPRF than lupus nephritis patients without small SBA (50% V.S. 0%, p<0.001, relative risk 82). Our data provide the first evidence of a strong association between IL-10PR and severe progression of lupus nephritis in human patients. In the future, a prospective genetic analysis of IL-10PR for patients with lupus nephritis is recommended. It might be helpful for physicians to identify the lupus nephritis subgroup with a high risk of developing RPRF early, because this might lead to a better therapy and prognosis for these patients.

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