HLA-linked rheumatoid arthritis.
HLA-linked rheumatoid arthritis.
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DOI：
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发表时间：
1994-10
影响因子：
9.8
通讯作者：
S. Hasstedt;D. Clegg;Linda Ingles;R. Ward
中科院分区：
文献类型：
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作者：
S. Hasstedt;D. Clegg;Linda Ingles;R. Ward
通过一对诊断为类风湿性关节炎(RA)的一级亲属确定了28个家系。在包括先证者在内的77个家系成员中确认了类风湿关节炎；在另外261个家系成员中证实没有疾病。家系成员进行了人类白细胞抗原的血清学分型。我们使用似然分析来统计分析与人类白细胞抗原相关的类风湿关节炎易感基因。该遗传模型假定与人类白细胞抗原紧密连锁。分析结果支持RA易感基因的存在，估计易感等位基因频率为2.16%，男性纯合子终生外显率为41%，女性纯合子终生外显率为48%。雄性为隐性遗传，雌性为近隐性遗传。此外，分析将78%的基因差异归因于兄弟姐妹共有的遗传或环境影响。这一分析中推断的遗传模式与先前关于类风湿关节炎的关联、连锁和家族聚集的研究是一致的。推测的与人类白细胞抗原相关的类风湿性关节炎易感基因座约占家族性类风湿性关节炎的一半，尽管它只占人群中类风湿性关节炎的五分之一。虽然其他基因可能解释了剩余的家族性类风湿性关节炎，但很大一部分类风湿关节炎病例可能是零星发生的。
Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed in 77 pedigree members including probands; the absence of disease was verified in an additional 261 pedigree members. Pedigree members were serologically typed for HLA. We used likelihood analysis to statistically characterize the HLA-linked RA susceptibility locus. The genetic model assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the susceptibility allele frequency as 2.16%, and estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. In addition, the analysis attributed 78% of the variance within genotypes to genetic or environmental effects shared by siblings. The genetic model inferred in this analysis is consistent with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-half of familial RA, although it accounts for only approximately one-fifth of the RA in the population. Although other genes may account for the remaining familial RA, a large portion of RA cases may occur sporadically.