Single-nucleotide polymorphisms in tumor necrosis factor receptor genes - Definition of novel haplotypes and racial/ethnic differences
Single-nucleotide polymorphisms in tumor necrosis factor receptor genes - Definition of novel haplotypes and racial/ethnic differences
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DOI：
10.1002/art.10463
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发表时间：
2002-08-01
影响因子：
--
通讯作者：
McNicholl, J
中科院分区：
文献类型：
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作者：
Bridges, SL;Jenq, G;McNicholl, J
客观的。表征患有类风湿性关节炎 (RA) 的非裔美国人、健康非裔美国人和健康白种人的肿瘤坏死因子受体 (TNFR) 基因中已知单核苷酸多态性 (SNP) 的等位基因频率。方法。在 108 名患有 RA 的非裔美国人、62 名健康非裔美国人和 59 名健康人中，对影响白种人家族性 RA 易感性的 1 个 TNFRSF1B SNP (196 G/T) 和 TNFRSF1A 基因 5' 侧翼区域的 3 个 SNP (-609G/T、-580A/G 和 -383A/C) 进行了基因分型。白种人。结果。患有 RA 的非洲裔美国人和健康的非洲裔美国人之间的 TNFRSF1A 等位基因频率没有差异。然而，健康的非洲裔美国人和健康的白种人之间的等位基因频率却存在显着差异：-609T 为 0 1 13 与 0.42，-580G 为 0.49 与 0，-383C 为 0.14 与 0。我们鉴定了由 3 个 TNFRSF1A SNP 定义的 4 个新单倍型，其分布在健康白种人和健康非洲裔美国人中显着不同（卡方检验 P = 0.000001）。患有 RA 的非裔美国人和健康的非裔美国人中 TNFRSF1B 196 基因型的频率相似，但健康的非裔美国人和健康的白种人之间存在差异 (P = 0.05)。结论。尽管我们观察到已知的 TNFR SNP 或单倍型与 RA 之间没有关联，但在两个基因座上均观察到显着的种族差异。将这些数据与其他公布的按种族划分的 TNFRSF1A 和 TNFRSF1B 基因型频率进行比较表明，非裔美国人、白种人和亚洲人群的分布存在显着差异。 TNFR SNP 频率中这些显着的种族/民族差异可能会影响家族性 RA、严重疾病或对 TNF 抑制剂的反应的可能性，并且可能具有重要的进化意义。
Objective. To characterize allele frequencies of known single-nucleotide polymorphisms (SNPs) in tumor necrosis factor receptor (TNFR) genes in African Americans with rheumatoid arthritis (RA), healthy African Americans, and healthy Caucasians.Methods. One TNFRSF1B SNP (196 G/T) that influences susceptibility to familial RA in Caucasians and 3 SNPs in the 5' flanking region of the TNFRSF1A gene (-609G/T, -580A/G,. and -383A/C) were genotyped in 108 African Americans with RA, 62 healthy African Americans, and 59 healthy Caucasians.Results. There were no differences in TNFRSF1A allele frequencies between African Americans with RA and healthy African Americans. Allele frequencies were strikingly different, however, between healthy African Americans and healthy Caucasians: 0 1 13 versus 0.42 for -609T, 0.49 versus 0 for -580G, and 0.14 versus 0 for -383C. We identified 4 novel haplotypes defined by the 3 TNFRSF1A SNPs, the distribution of which was markedly different in healthy Caucasians and healthy African Americans (P = 0.000001 by chi-square test). The frequencies of the TNFRSF1B 196 genotypes were similar in African Americans with RA and healthy African Americans but differed between healthy African Americans and healthy Caucasians (P = 0.05).Conclusion. Although we observed no associations between known TNFR SNPs or haplotypes and RA, significant racial differences were observed at both loci. Comparison of these data with other published frequencies of TNFRSF1A and TNFRSF1B genotypes according to race suggests that the distribution in African American, Caucasian, and Asian populations differs significantly. These striking racial/ethnic differences in TNFR SNP frequencies may influence the likelihood of familial RA, severe disease, or response to TNF inhibitors and may have important evolutionary implications.