Laivoranta-Nyman S, Luukkainen R, Hakala M, Hannonen P, Möttönen T, Yli-Kerttula U, Ilonen J, Toivanen A
Turku Immunology Centre, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland.
Ann Rheum Dis. 2001 Apr;60(4):413-5. doi: 10.1136/ard.60.4.413.
To determine whether there are genetic differences between female and male patients with familial rheumatoid arthritis (RA).
45 men and 119 women from 78 families with RA who all had at least one first degree relative with RA were compared. HLA-DRB1 alleles were analysed, including DRB104 subtypes and associations of DRB104 haplotypes with DQB10301 or DQB10302 alleles, the age of the patients at disease onset, the presence of rheumatoid factor (RF), joint erosions, and rheumatoid nodules.
HLA-DRB1*13 allele (the subtype allele of DR6, reported to be protective against the development of RA) was found in 14/119 (12%) of female but in none of the male patients (p=0.036). The HLA-DR4 allele was found slightly more often in men than women patients with familial RA (31/45 (69%) v 75/119 (63%), NS). Men were also more often RF positive than women (44/45 (98%) v 98/117 (84%); p=0.031). On the other hand, the mean age at onset of RA was significantly lower in the female group (40.4 years) than in men (46.6 years, p=0.0044).
The results indicate that there is stronger genetic background in familial male than female patients with RA in the genetic susceptibility defined by the studied HLA antigens. However, the earlier age of onset of the disease in female group and the increased proportion of women with RA indicate that there are additional sex related predisposing factors enhanced in familial cases.
确定家族性类风湿关节炎(RA)的女性和男性患者之间是否存在基因差异。
对来自78个RA家庭的45名男性和119名女性进行比较,这些家庭中均至少有一名一级亲属患有RA。分析HLA - DRB1等位基因,包括DRB104亚型以及DRB104单倍型与DQB10301或DQB10302等位基因的关联,患者发病时的年龄、类风湿因子(RF)的存在情况、关节侵蚀以及类风湿结节。
在119名女性患者中有14名(12%)发现了HLA - DRB1*13等位基因(DR6的亚型等位基因,据报道对RA的发生有保护作用),而男性患者中未发现(p = 0.036)。在家族性RA患者中,男性比女性更常发现HLA - DR4等位基因(31/45(69%)对75/119(63%),无显著差异)。男性RF阳性的比例也高于女性(44/45(98%)对98/117(84%);p = 0.031)。另一方面,女性组RA发病的平均年龄(40.4岁)显著低于男性(46.6岁,p = 0.0044)。
结果表明,在所研究的HLA抗原定义的遗传易感性方面,家族性RA男性患者比女性患者具有更强的遗传背景。然而,女性组疾病发病年龄较早以及RA女性患者比例增加表明,在家族性病例中存在其他与性别相关的易感因素。