The contribution of SAA1 polymorphisms to Familial Mediterranean fever susceptibility in the Japanese population.

Familial Mediterranean Fever (FMF) has traditionally been considered to be an autosomal-recessive disease, however, it has been observed that substantial numbers of patients with FMF possess only 1 demonstrable MEFV mutation. The clinical profile of familial Mediterranean fever (FMF) may be influenced by MEFV allelic heterogeneity and other genetic and/or environmental factors. In view of the inflammatory nature of FMF, we investigated whether serum amyloid A (SAA) and interleukin-1 beta (IL-1β) gene polymorphisms may affect the susceptibility of Japanese patients with FMF. The genotypes of the -13C/T SNP in the 5′-flanking region of the SAA1 gene and the two SNPs within exon 3 of SAA1 (2995C/T and 3010C/T polymorphisms) were determined in 83 Japanese patients with FMF and 200 healthy controls. The same samples were genotyped for IL-1β-511 (C/T) and IL-1 receptor antagonist (IL-1Ra) variable number of tandem repeat (VNTR) polymorphisms. There were no significant differences between FMF patients and healthy subjects in the genotypic distribution of IL-1β -511 (C/T), IL-1Ra VNTR and SAA2 polymorphisms. The frequencies of SAA1.1 allele were significantly lower (21.7% versus 34.0%), and inversely the frequencies of SAA1.3 allele were higher (48.8% versus 37.5%) in FMF patients compared with healthy subjects. The frequency of -13T alleles, associated with the SAA1.3 allele in the Japanese population, was significantly higher (56.0% versus 41.0%, p = 0.001) in FMF patients compared with healthy subjects. Our data indicate that SAA1 gene polymorphisms, consisting of -13T/C SNP in the 5′-flanking region and SNPs within exon 3 (2995C/T and 3010C/T polymorphisms) of SAA1 gene, are associated with susceptibility to FMF in the Japanese population.

家族性地中海热（FMF）传统上被认为是一种常染色体隐性疾病，然而，据观察，大量的FMF患者仅具有1个可证实的MEFV突变。家族性地中海热（FMF）的临床特征可能受MEFV等位基因异质性以及其他遗传和/或环境因素的影响。 鉴于FMF的炎症性质，我们研究了血清淀粉样蛋白A（SAA）和白细胞介素 - 1β（IL - 1β）基因多态性是否可能影响日本FMF患者的易感性。对83例日本FMF患者和200名健康对照者测定了SAA1基因5′侧翼区的 - 13C/T单核苷酸多态性（SNP）以及SAA1外显子3内的两个SNP（2995C/T和3010C/T多态性）的基因型。对相同的样本进行了IL - 1β - 511（C/T）和IL - 1受体拮抗剂（IL - 1Ra）可变数目串联重复（VNTR）多态性的基因分型。在IL - 1β - 511（C/T）、IL - 1Ra VNTR和SAA2多态性的基因型分布方面，FMF患者和健康受试者之间没有显著差异。与健康受试者相比，FMF患者中SAA1.1等位基因的频率显著较低（21.7%对34.0%），而SAA1.3等位基因的频率则相反较高（48.8%对37.5%）。在日本人群中与SAA1.3等位基因相关的 - 13T等位基因的频率在FMF患者中显著高于健康受试者（56.0%对41.0%，p = 0.001）。 我们的数据表明，由SAA1基因5′侧翼区的 - 13T/C SNP以及SAA1基因外显子3内的SNP（2995C/T和3010C/T多态性）组成的SAA1基因多态性与日本人群对FMF的易感性相关。