Study on the influence of polymorphisms of SAA1 and SAA2 gene on the development of AA-amyloidosis.

为了探讨SAA基因多态性是否与AA-淀粉样变性的发生有关，我们检测了43例AA-淀粉样变性患者(淀粉样变性患者)和77例发病时间小于5年的类风湿性关节炎患者(早期RA患者)的SAA1和SAA2基因频率。我们还比较了90名韩国人、95名台湾人和103名日本人SAA1基因座的基因频率。淀粉样变性人群中γ/γ基因和γ等位基因频率显著高于早期RA人群(34.9%vs7.8%和58.1%vs33.8%，c2检验p=0.0001)。韩国人、台湾人和日本人的γ等位基因频率分别为41.6%、35.6%和37.4%。AA-淀粉样变性的潜伏期在γ等位基因数目较少的患者中显著延长(Spearman‘s相关系数：-0.42p&lt0.05)。另一方面，在AA-淀粉样变性诊断前2年内，在γ等位基因数目较多的患者中，C反应蛋白水平显著升高(Spearman‘s相关系数：0.34；p&lt；0.05)。未发现淀粉样变性与SAA2基因多态之间的显著关联。我们推测，等位基因SAA1γ可能通过影响RA炎症的严重程度，使RA患者易患淀粉样变性。

To examine whether polymorphism at the SAA loci is associated with the development of AA-amyloidosis, we determined the genotypes at the SAA1 and SAA2 loci in 43 AA-amyloidosis patients (amyloidosis population) and 77 patients with rheumatoid arthritis who had been ill for less than 5 years (early RA population). We also compared the frequencies of the genotypes at the SAA1 locus among 90 Korean, 95 Taiwanese and 103 Japanese healthy subjects. The frequencies of the γ/γ genotype and γ alleles at the SAA1 locus were significantly higher in the amyloidosis population than in the early RA population (34.9% versus 7.8% and 58.1% versus 33.8%, c2 test p=0.0001). The frequencies of the γ allele at the SAA1 locus in Koreans, Taiwanese and Japanese were 41.6%, 35.6% and 37.4%, respectively. The length of the latent period of AA-amyloidosis was significantly longer in the patients with smaller numbers of the γ allele at SAA1 locus (Spearman's correlation coefficient : -0.42 ; p<0.05). On the other hand, the mean CRP level during 2 years prior to the diagnosis of AA-amyloidosis was significantly higher in the patiesnts with larger numbers of the γ allele at the SAA1 locus (Spearman's correlation coefficient : 0.34 ; p<0.05). No significant association was found between amyloidosis and polymorphism at the SAA2 locus. We postulate that the allele SAA1 γ renders an RA patient susceptible to amyloidosis, possibly by affecting the severity of inflammation in RA.