Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort
Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort
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DOI：
10.1038/sj.gene.6364383
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发表时间：
2007-06-01
影响因子：
5
通讯作者：
Criswell, L. A.
中科院分区：
文献类型：
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作者：
Thorburn, C. M.;Prokunina-Olsson, L.;Criswell, L. A.
我们评估了PDCD1内5个单核苷酸多态性（SNPs）以及由这些SNPs定义的单倍型在系统性红斑狼疮（SLE）和特定亚表型（肾炎、抗磷脂抗体阳性、关节炎和双链DNA阳性）发生中的作用，这些亚表型在1036例多种族美国患者队列中。基于家庭的分析进行了844个单一的家庭，从四个种族群体（高加索人，亚洲人，西班牙裔和非洲裔美国人）。受试者的基因分型为5个“标签”SNP（从15个中选择），以提供所有主要种族群体的完整遗传信息。我们采用传递不平衡检验通过等位基因或单倍型评估SLE的风险，并对SLE病例进行多元Logistic回归分析以检查与特定亚表型的关联。在基于家族的分析中，包含PD1.3A等位基因的单倍型与白人家族中的SLE易感性显著相关（P = 0.01）。在西班牙裔家庭中，两个新的SNP与SLE风险相关（P = 0.005和0.01）。在多因素logistic回归分析中，5个单倍型与不同种族群体中的特定亚表型相关。这些结果表明，PDCD1基因变异影响SLE的风险和表达，这些协会根据种族背景而有所不同。
We evaluated the roles of five single-nucleotide polymorphisms (SNPs) within PDCD1, and haplotypes defined by these SNPs, for the development of systemic lupus erythematosus (SLE) and specific sub-phenotypes (nephritis, antiphospholipid antibody positive, arthritis and double-stranded DNA positive) within a multiethnic US cohort of 1036 patients. Family based analyses were performed using 844 simplex families from four ethnic groups (Caucasian, Asian, Hispanic and African American). Subjects were genotyped for five 'tag' SNPs (selected from 15) to provide complete genetic information in all main ethnic groups. We employed transmission disequilibrium testing to assess risk for SLE by allele or haplotype, and multiple logistic regression analysis of SLE cases to examine associations with specific sub-phenotypes. In family based analyses, a haplotype containing the PD1.3A allele was significantly associated with SLE susceptibility among Caucasian families (P = 0.01). Among Hispanic families, two novel SNPs were associated with SLE risk (P = 0.005 and 0.01). In multivariate logistic regression analyses, five haplotypes were associated with specific sub-phenotypes among the different ethnic groups. These results suggest that PDCD1 genetic variation influences the risk and expression of SLE and that these associations vary according to ethnic background.