Role of an intronic polymorphism in the PDCD1 gene with the risk of sporadic systemic lupus erythematosus and the occurrence of antiphospholipid antibodies
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 allele 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.
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