Role of an intronic polymorphism in the PDCD1 gene with the risk of sporadic systemic lupus erythematosus and the occurrence of antiphospholipid antibodies
Role of an intronic polymorphism in the PDCD1 gene with the risk of sporadic systemic lupus erythematosus and the occurrence of antiphospholipid antibodies
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DOI：
10.1007/s00439-004-1172-0
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发表时间：
2004-10-01
期刊：
影响因子：
5.3
通讯作者：
Kamboh, MY
中科院分区：
文献类型：
--
作者：
Sanghera, DK;Manzi, S;Kamboh, MY
最近，程序性细胞死亡1（PDCD 1）基因内含子4（G/A）的多态性被证明与欧洲、欧洲、美国和墨西哥血统的家族性和散发性患者的系统性红斑狼疮（SLE）风险相关。在这项研究中，我们研究了这种多态性在311例SLE患者（276名欧洲裔美国人和35名非洲裔美国人）和390名年龄匹配的健康对照（359名欧洲裔美国人和31名非洲裔美国人）中的作用。在欧洲裔美国人对照组中，A等位基因的频率显著高于非洲裔美国人对照组（0.107 vs. 0.048; P=0.046）。在欧洲裔美国人（0.107 vs. 0.129; P=0.84）或非洲裔美国人（0.048 vs. 0.100; P=0.25）队列中，SLE病例和对照组之间的A等位基因频率无显著差异。然而，在logistic回归分析中调整抗磷脂抗体（阿帕）的状态后，与PDCD 1多态性相关的SLE风险具有统计学意义。A等位基因携带者之间的APA调整的比值比（OR）（AA+AG基因型）与GG基因型相比，在欧洲裔美国人中显示与SLE风险适度相关（OR=1.52，95% CI：1.02-2.27; P=0.039），非裔美国人（OR=2.89，95%CI：0.61-13.76; P=0.183），种族合并样本（OR=1.59，95%CI：1.08-2.34; P=0.019）。此外，我们观察到A等位基因携带者在对照组（OR=0.399，95% CI：0.19-0.82; P=0.0098）和SLE患者（OR=0.566，95% CI：0.32-1.01; P=0.054）中均能保护阿帕的发生。我们的数据表明PDCD 1基因内含子4的多态性影响阿帕的发生，并可能轻微改变散发性SLE的风险。
Recently, a polymorphism in intron 4 (G/A) of the programmed cell death 1 (PDCD1) gene was shown to be associated with systemic lupus erythematosus (SLE) risk in familial and sporadic patients of European, European American, and Mexican origin. In this investigation, we examined the role of this polymorphism in 311 SLE patients (276 European Americans and 35 African Americans) and 390 age-matched healthy controls (359 European Americans and 31 African Americans). The frequency of the A allele was significantly higher in European American controls than in African American controls (0.107 vs. 0.048; P=0.046). There was no significant difference in the frequency of the A allele between SLE cases and controls in either the European American (0.107 vs. 0.129; P=0.84) or African American (0.048 vs. 0.100; P=0.25) cohort. However, after adjustment for the status of the antiphospholipid antibodies (APA) in the logistic regression analysis, the risk for SLE associated with the PDCD1 polymorphism was statistically significant. The APA-adjusted odds ratio (OR) between A allete carriers (AA+AG genotypes) versus the GG genotype showed a modest association with SLE risk in European Americans (OR=1.52, 95% CI: 1.02-2.27; P=0.039), African Americans (OR=2.89, 95% CI: 0.61-13.76; P=0.183), and the ethnicity-combined sample (OR=1.59, 95% CI: 1.08-2.34; P=0.019). Furthermore, we observed that the A allele carriers were protected against the occurrence of APA in both controls (OR=0.399, 95% CI: 0.19-0.82; P=0.0098) and SLE cases (OR=0.566, 95% CI: 0.32-1.01; P=0.054). Our data indicate polymorphism in intron 4 of the PDCD1 gene affects the occurrence of APA and may slightly modify the risk of sporadic SLE.