Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-alpha-238 and-308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long-term follow-up Brazilian study
Human leukocyte antigen (HLA) and single nucleotide polymorphisms (SNPs) tumor necrosis factor (TNF)-alpha-238 and-308 as genetic markers of susceptibility to psoriasis and severity of the disease in a long-term follow-up Brazilian study
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DOI：
10.1111/j.1365-4632.2010.04465.x
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发表时间：
2010-10-01
影响因子：
3.6
通讯作者：
Kraemer, Maria Helena
中科院分区：
文献类型：
--
作者：
Magalhaes, Renata Ferreira;Biral, Ana Cristina;Kraemer, Maria Helena
背景 银屑病最强的遗传标记是 Cw*06。肿瘤坏死因子 (TNF)-α 启动子区域的多态性，特别是在 -238 和 -308 位用腺嘌呤取代鸟嘌呤，与高加索人群中较高的 TNF-α 产生和较高的牛皮癣风险相关，但在亚洲人中未发现。我们对 69 名 I 型银屑病患者和 70 名对照者进行了一项病例对照研究，描述了轻度或重度疾病 10 年随访中的临床进展，并确定了 HLA I 类、II 类和 TNF 单核苷酸多态性 (SNP) -238 和 -308 多态性，以证明这些多态性是否可能是巴西人银屑病易感性或疾病严重程度的遗传风险。 方法使用PCR/SSP 鉴定多态性。使用Fisher检验比较等位基因、基因型和单倍型频率。结果发现男性患者的疾病更严重。可能表明等位基因 B*37、Cw*06、Cw*12 和 DRB1*07 与严重病程相关，而 B*57 与轻度疾病相关。在 TNF SNP 多态性频率方面，患者和对照之间没有发现统计学差异。本研究指出，重症患者中 TNF-238 G/G 基因型频率较高（OR：3.21；CI：1.06-9.71；P = 0.04）。 结论 在巴西患者中，TNF-α SNP 的多态性似乎并不比已知的 Cw*06 更重要，是银屑病的遗传危险因素，但这些标志物可能与临床表现有关。
Background The strongest genetic marker for psoriasis is Cw*06. Polymorphisms in the tumor necrosis factor (TNF)-alpha promoter region, especially replacement of guanine with adenine in positions -238 and -308 are related to higher TNF-alpha production and higher risk for psoriasis in Caucasoid populations, not found in Asians. We performed a case-control study of 69 patients with psoriasis type I and 70 controls, characterized clinical progression along 10-years of follow-up in mild or severe disease and determined HLA class I, II, and TNF single nucleotide polymorphisms (SNPs) -238 and -308 polymorphisms to demonstrate whether these polymorphisms may be genetic risk for susceptibility to psoriasis or severity of the disease in Brazilians.Methods Polymorphisms were identified using PCR/SSP. Alleles, genotypes, and haplotypes frequencies were compared using Fisher's test.Results More severe disease was found in male patients. It may be suggested that alleles B*37, Cw*06, Cw*12, and DRB1*07 were associated with severe disease course, while B*57 with mild disease. No statistical difference was found between the patients and controls regarding polymorphisms frequencies in TNF SNPs. This study pointed to a higher TNF-238 G/G genotype frequency (OR: 3.21; CI: 1.06-9.71; P = 0.04) in the group with severe disease.Conclusions Polymorphisms in the TNF-alpha SNPs do not seem to be a more important genetic risk factor for psoriasis than the already known Cw*06 in Brazilian patients, but these markers may be related to clinical manifestations.