Broen J, Gourh P, Rueda B, Coenen M, Mayes M, Martin J, Arnett F C, Radstake T R D J
Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
Arthritis Rheum. 2009 Dec;60(12):3815-20. doi: 10.1002/art.24964.
To investigate the possible role of the FAS -670A>G functional polymorphism in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype.
A total of 2,900 SSc patients and 3,186 healthy controls were included in this study. We analyzed the genotype and allele frequencies of the FAS -670A>G polymorphism in 9 distinct ethnic cohorts, including 6 cohorts of European ancestry (a Spanish cohort of 228 SSc patients and 265 controls, a Dutch cohort of 203 SSc patients and 277 controls, a German cohort of 313 SSc patients and 247 controls, an Italian cohort of 323 SSc cases and 89 controls, a British cohort of 269 SSc patients, and a Swedish cohort of 182 patients) and 3 distinct ethnic cohorts from the US (a cohort of 1,047 white patients and 692 controls, a cohort of 159 Hispanic patients and 137 controls, and a cohort of 176 black SSc patients and 194 controls). Genotyping was performed using a TaqMan 5' allelic discrimination assay.
In the British, Italian, and American white cohorts we observed an association of the FAS -670G allele with limited cutaneous SSc (lcSSc) (odds ratios [ORs] 1.25, 1.43, and 1.18, respectively). A meta-analysis comprising all 9 cohorts revealed an association of both the FAS -670G allele (OR 1.10) and the FAS -670GG genotype (OR 1.13) with the lcSSc phenotype. In a meta-analysis including only white subjects, both the FAS -670G allele and the FAS -670GG genotype remained associated with lcSSc (allele OR 1.12; genotype OR 1.16). In addition, a recessive model of the -670GG genotype exhibited a strong association with SSc, lcSSc, and anticentromere antibody-positive lcSSc (OR 1.23, OR 1.33, and OR 1.45, respectively).
Our data show that the FAS -670A>G polymorphism plays a role in lcSSc susceptibility. A similar trend has been observed in other autoimmune diseases.
研究FAS -670A>G功能多态性在系统性硬化症（SSc）易感性或临床表型的遗传易感性中可能发挥的作用。
本研究共纳入2900例SSc患者和3186例健康对照。我们分析了9个不同种族队列中FAS -670A>G多态性的基因型和等位基因频率，其中包括6个欧洲血统队列（一个西班牙队列，有228例SSc患者和265例对照；一个荷兰队列，有203例SSc患者和277例对照；一个德国队列，有313例SSc患者和247例对照；一个意大利队列，有323例SSc病例和89例对照；一个英国队列，有269例SSc患者；一个瑞典队列，有182例患者）以及来自美国的3个不同种族队列（一个队列有1047例白人患者和692例对照；一个队列有159例西班牙裔患者和137例对照；一个队列有176例黑人SSc患者和194例对照）。使用TaqMan 5'等位基因鉴别分析进行基因分型。
在英国、意大利和美国白人队列中，我们观察到FAS -670G等位基因与局限性皮肤型SSc（lcSSc）相关（优势比[OR]分别为1.25、1.43和1.18）。对所有9个队列进行的荟萃分析显示，FAS -670G等位基因（OR 1.10）和FAS -670GG基因型（OR 1.13）均与lcSSc表型相关。在仅包括白人受试者的荟萃分析中，FAS -670G等位基因和FAS -670GG基因型仍与lcSSc相关（等位基因OR 1.12；基因型OR 1.16）。此外，-670GG基因型的隐性模型与SSc、lcSSc和抗着丝点抗体阳性的lcSSc呈强相关（OR分别为1.23、1.33和1.45）。
我们的数据表明，FAS -670A>G多态性在lcSSc易感性中起作用。在其他自身免疫性疾病中也观察到了类似趋势。
