A NOVEL ALLELIC VARIANT OF SERUM AMYLOID-A, SAA1-GAMMA - GENOMIC EVIDENCE, EVOLUTION, FREQUENCY, AND IMPLICATION AS A RISK FACTOR FOR REACTIVE SYSTEMIC AA-AMYLOIDOSIS
A NOVEL ALLELIC VARIANT OF SERUM AMYLOID-A, SAA1-GAMMA - GENOMIC EVIDENCE, EVOLUTION, FREQUENCY, AND IMPLICATION AS A RISK FACTOR FOR REACTIVE SYSTEMIC AA-AMYLOIDOSIS
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DOI：
10.1093/hmg/4.6.1083
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发表时间：
1995-06-01
影响因子：
3.5
通讯作者：
SHIRASAWA, H
中科院分区：
文献类型：
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作者：
BABA, S;MASAGO, SA;SHIRASAWA, H
反应性系统性淀粉样变性，也称为AA-淀粉样变性，是常见慢性炎症性疾病如类风湿性关节炎的罕见致命并发症。已经提出，除了血清前体蛋白血清淀粉样蛋白A（SAA）水平的持续升高之外，尚未确定的因素对于AA-淀粉样变性的发展也是重要的。在这项工作中，我们显示了人类SAA的新等位基因变体的基因组证据，SAA 1 gamma，我们最近在蛋白质水平上鉴定了它，SAA 1 gamma [Ala（52）（GCC），Ala（57）（GCG）]与SAA 1 alpha [瓦尔（52）（GTC），Ala（57）（GCG）]仅在一个碱基上不同，表明存在单点突变，另一方面，SAA 1 beta [Ala（52）（GCC），瓦尔（57）（GTG）]不仅有一个，但是在附近的内含子中存在另外的差异，并且该部分与SAA 2基因相同，这表明SAA 1和SAA 2基因之间存在交换。此外，我们报道，在AA-淀粉样变性的类风湿关节炎患者和对照人群中观察到的SAA 1等位基因数量存在显著差异（χ 2 = 1.25）。11.59，P = 0.003），AA-淀粉样蛋白组中γ等位基因频率较高在AA-淀粉样蛋白组中，SAA 1基因型分布也有显著差异（χ（5）（2）= 14.63，p = 0.012），γ/γ纯合子频率增加（0.60 vs，0.18），因此，我们的研究结果表明，这种新的等位基因变异可能是AA-淀粉样变性发展的重要危险因素，
Reactive systemic amyloidosis, also called AA-amyloidosis is a rare fatal complication of common chronic inflammatory diseases such as rheumatoid arthritis, It has been proposed that as yet undefined factors other than persistent elevation of serum level of the precursor protein, serum amyloid A (SAA), are also important for the development of AA-amyloidosis, In this work we show genomic evidence for a novel allelic variant of human SAA, SAA1 gamma, which we have recently identified at the protein level, The SAA1 gamma [Ala(52)(GCC), Ala(57)(GCG)] differed from SAA1 alpha [Val(52)(GTC), Ala(57)(GCG)] only at one base, indicating a single point mutation, On the other hand, SAA1 beta [Ala(52)(GCC), Val(57)(GTG)] had not only one, but additional differences in a nearby intron and this portion was identical to the SAA2 gene, suggesting a crossing-over between the SAA1 and SAA2 genes, Furthermore, we report that there was a significant difference in the observed numbers of SAA1 alleles between rheumatoid arthritis patients with AA-amyloidosis and the control population (chi(2)(2) = 11.59, P = 0.003) with a higher frequency of gamma-allele in the AA-amyloid group (0.70 vs, 0.37), There was also a notable difference in the distribution of SAA1 genotypes (chi(5)(2) = 14.63, p = 0.012) with an increased frequency of gamma/gamma-homozygotes in the AA-amyloid group (0.60 vs, 0.18), Thus our findings indicate that this novel allelic variant may be an important risk factor for the development of AA-amyloidosis,