Wasfi Y S, Silveira L J, Jonth A, Hokanson J E, Fingerlin T, Sato H, Parsons C E, Lympany P, Welsh K, du Bois R M, Newman L S, Maier L A
Merck Research Laboratories, Upper Gwynedd, PA, USA.
Tissue Antigens. 2008 Jul;72(1):39-48. doi: 10.1111/j.1399-0039.2008.01060.x.
Apoptosis may perpetuate some forms of inflammation. Of the apoptotic pathway proteins, Fas is particularly overexpressed in sarcoidosis. We hypothesized that Fas promoter single nucleotide polymorphisms (SNPs) contribute to the development and severity of sarcoidosis. Associations of known Fas promoter SNPs (-670, -690 and -1377) and deduced haplotypes with sarcoidosis and sarcoidosis severity were evaluated using matched case-control (n = 656 pairs) and case-comparison (n = 656) studies, respectively, using conditional logistic regression. Hardy-Weinberg equilibrium was confirmed for all three polymorphisms in African-Americans (AA), and for the -670 and -1377 in whites. Genotype and allele frequencies were significantly different between whites and AA. Race-stratified analysis revealed that a common haplotype, -1377G/-690T/-670G, was associated with sarcoidosis [odds ratio (OR) = 1.78, P = 0.05] only in AA. The haplotype -1377G/-690C/-670A was negatively associated with sarcoidosis (OR = 0.39, P = 0.03) only in AA. In conclusion, the consistency of these findings suggests that Fas promoter genetic variants may be related to sarcoidosis disease risk in AA.
细胞凋亡可能会使某些形式的炎症持续存在。在细胞凋亡通路蛋白中，Fas在结节病中尤其过度表达。我们推测Fas启动子单核苷酸多态性（SNP）与结节病的发生和严重程度有关。分别使用匹配病例对照研究（n = 656对）和病例比较研究（n = 656），通过条件逻辑回归评估已知的Fas启动子SNP（-670、-690和-1377）以及推导的单倍型与结节病及其严重程度的关联。在非裔美国人（AA）中，所有三种多态性均符合哈迪-温伯格平衡，在白人中，-670和-1377符合哈迪-温伯格平衡。白人和AA之间的基因型和等位基因频率存在显著差异。种族分层分析显示，仅在AA中，一种常见的单倍型-1377G/-690T/-670G与结节病相关[比值比（OR）= 1.78，P = 0.05]。单倍型-1377G/-690C/-670A仅在AA中与结节病呈负相关（OR = 0.39，P = 0.03）。总之，这些发现的一致性表明Fas启动子基因变异可能与AA患结节病的风险有关。
