Okuda Y, Yamada T, Takasugi K, Takeda M, Nanba S, Onishi M, Miyamoto T, Inoue Y
Department of Internal Medicine, Center for Rheumatic Diseases, Dohgo Spa Hospital, Ehime.
Ryumachi. 1999 Feb;39(1):3-10.
To examine the relationship between polymorphism of serum amyloid A (SAA) 1, SAA 2 and Apolipoprotein E (Apo E) and susceptibility to AA amyloidosis (AA) in rheumatoid arthritis (RA).
We compared the frequencies of SAA 1 alleles (alpha, beta, gamma), SAA 2 alleles (alpha, beta) and apo E alleles (epsilon 2, epsilon 3, epsilon 4) in AA-positive RA with those in AA-negative RA. Each isotype was analyzed by the following method: SAA 1 and SAA 2 by PCR-RFLP and Apo E by Western blotting method. Blood samples were obtained from 50 AA-positive RA patients with SAA 1 isotype, 50 AA-negative RA patients with SAA 1 isotype, 27 AA-positive RA patients with SAA 2 isotype, and 26 AA-negative RA patients with SAA 2 isotype, respectively. Likewise, Apo E isotype was determined by withdrawing blood samples from 61 AA-positive RA cases and 51 AA-negative RA cases.
In AA-positive RA, each frequency of three different alleles of SAA 1, i.e., alpha, beta and gamma was 15%, 32% and 53%, while it was 32%, 28% and 40% in AA-negative RA. The allelic distribution between AA-positive RA group and AA-negative RA group was significantly different (P = 0.00163) with a lower frequency of alpha allele and a higher gamma allele frequency observed in AA-positive RA group. The frequency of each SAA 2 alleles (alpha & beta) was almost identical: 88.9% and 11.1% in AA-positive RA versus 90.4% and 9.6% in AA-negative RA with p value of 0.8007. Each frequency of three different Apo E alleles (epsilon 2, epsilon 3 & epsilon 4) was 4.9%, 85.2% and 9.8% in AA-positive RA, while in AA-negative RA it was 7.8%, 86.3% and 5.9%, respectively. The AA-positive RA group showed a slightly higher prevalence of epsilon 4 allele than the AA-negative RA group, yet the difference did not reach statistical significance (P = 0.3969).
These results suggest the possibilities that SAA 1 alpha may be working protectively against and SAA 1 gamma provocatively for the development of AA amyloidosis in RA. However, there was no significant association between SAA 2 isotype patterns and the development of AA amyloidosis in RA. Furthermore, there was no discernible association between AA amyloidosis in RA and Apo E 4 isotype.
研究血清淀粉样蛋白A(SAA)1、SAA 2基因多态性及载脂蛋白E(Apo E)与类风湿关节炎(RA)患者发生AA型淀粉样变性(AA)易感性之间的关系。
比较AA阳性RA患者与AA阴性RA患者中SAA 1等位基因(α、β、γ)、SAA 2等位基因(α、β)及Apo E等位基因(ε2、ε3、ε4)的频率。每种同种型采用以下方法分析:SAA 1和SAA 2采用聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP),Apo E采用蛋白质印迹法。分别从50例SAA 1同种型的AA阳性RA患者、50例SAA 1同种型的AA阴性RA患者、27例SAA 2同种型的AA阳性RA患者和26例SAA 2同种型的AA阴性RA患者中采集血样。同样,通过从61例AA阳性RA患者和51例AA阴性RA患者中采集血样来确定Apo E同种型。
在AA阳性RA患者中,SAA 1的三种不同等位基因α、β和γ的频率分别为15%、32%和53%,而在AA阴性RA患者中分别为32%、28%和40%。AA阳性RA组与AA阴性RA组之间的等位基因分布存在显著差异(P = 0.00163),在AA阳性RA组中观察到α等位基因频率较低,γ等位基因频率较高。SAA 2各等位基因(α和β)的频率几乎相同:AA阳性RA患者中为88.9%和11.1%,AA阴性RA患者中为90.4%和9.6%,P值为0.8007。AA阳性RA患者中Apo E的三种不同等位基因(ε2、ε3和ε4)的频率分别为4.9%、85.2%和9.8%,而在AA阴性RA患者中分别为7.8%、86.3%和5.9%。AA阳性RA组中ε4等位基因的患病率略高于AA阴性RA组,但差异未达到统计学意义(P = 0.3969)。
这些结果提示,SAA 1α可能对RA患者发生AA型淀粉样变性具有保护作用,而SAA 1γ可能具有促发作用。然而,SAA 2同种型模式与RA患者发生AA型淀粉样变性之间无显著关联。此外,RA患者的AA型淀粉样变性与Apo E 4同种型之间无明显关联。