The (CCTTT) n pentanucleotide repeat polymorphism in the inducible nitric oxide synthase gene promoter and the risk of psoriasis in Taiwanese
The (CCTTT) n pentanucleotide repeat polymorphism in the inducible nitric oxide synthase gene promoter and the risk of psoriasis in Taiwanese
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DOI：
10.1007/s00403-015-1542-6
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发表时间：
2015-07-01
影响因子：
3
通讯作者：
Hsu, Lung-An
中科院分区：
文献类型：
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作者：
Chang, Ya-Ching;Wu, Wei-Ming;Hsu, Lung-An
最近，全基因组关联研究发现了一个新的银屑病易感基因位点标记的两个单核苷酸多态性（SNPs）rs 4795067和rs 28998802，这两个都是在诱导型一氧化氮合酶（iNOS）基因的内含子区域。本研究旨在评估中国台湾地区银屑病患者iNOS基因启动子区（CCTTT）（n）五核苷酸重复多态性的作用。总共，280例银屑病患者和512名对照组进行了分析的iNOS微卫星多态性的聚合酶链反应的存在。根据（CCTTT）（n）重复数将等位基因分为S和L等位基因，其中具有千分之一货币符号13重复的等位基因被指定为S，具有千分之一日元14重复的等位基因被指定为L等位基因。等位基因频率和基因型分布在对照组和银屑病组之间差异有统计学意义（P = 0.040和0.014）。校正年龄、性别、体重指数、吸烟、糖尿病和高血压后，LL基因型携带者患银屑病的可能性是非携带者的0.38倍（95%置信区间0.16-0.95）（P = 0.038）。启动子测定表明，HaCaT细胞中iNOS启动子活性与（CCTTT）（n）的重复数平行增加。约70%的研究受试者进行了rs 4795067和rs 28998802基因分型。rs 4795067与微卫星L/S等位基因分类连锁不平衡。iNOS微卫星与银屑病的关联独立于这些已知的iNOS变体。我们的研究结果表明，诱导型一氧化氮合酶微卫星可能有助于遗传背景的银屑病在中国台湾地区的患者。
Recently, genome-wide association studies identified a novel psoriasis susceptibility locus tagged by two single-nucleotide polymorphisms (SNPs) rs4795067 and rs28998802, both of which are in the intronic region of inducible nitric oxide synthase (iNOS) gene. This study aimed to assess the role of (CCTTT) (n) pentanucleotide repeat polymorphisms in the promoter region of iNOS gene in Chinese-Taiwanese patients with psoriasis. In total, 280 patients with psoriasis and 512 control subjects were analyzed for the presence of the iNOS microsatellite polymorphism by polymerase chain reactions. The alleles were classified as S and L alleles according to the number of (CCTTT) (n) repeats, with the alleles with a parts per thousand currency sign13 repeats designated as S and alleles with a parts per thousand yen14 repeats designated as L alleles. The distribution of allele frequencies and genotypes was significantly different between the control and psoriasis groups (P = 0.040, and 0.014, respectively). After adjustment for age, sex, body mass index, smoking, diabetes, and hypertension, carriers of the LL genotype were 0.38 (95 % confidence interval 0.16-0.95) times less likely than non-carriers to have psoriasis (P = 0.038). The promoter assays demonstrated that the iNOS promoter activity increases in parallel with the repeat number of (CCTTT) (n) in HaCaT cells. Approximately 70 % of the study subjects were genotyped for rs4795067 and rs28998802. The rs4795067 is in linkage disequilibrium with the microsatellite L/S allelic classification. The association of iNOS microsatellite with psoriasis is independent of these known iNOS variants. Our results suggest that the iNOS microsatellite may contribute to the genetic background of psoriasis in Chinese-Taiwanese patients.