A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population.
A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population.
复制标题
SPINK5基因的功能多态性与中国汉族人群哮喘相关
DOI：
10.1186/1471-2350-10-59
复制
发表时间：
2009-06-17
影响因子：
--
通讯作者：
Gong Y
中科院分区：
文献类型：
--
作者：
Liu Q;Xia Y;Zhang W;Li J;Wang P;Li H;Wei C;Gong Y
背景
SPINK 5突变导致内瑟顿综合征，这是一种罕见的隐性皮肤病，伴有严重的特应性表现，包括特应性皮炎、过敏性鼻炎、哮喘、高血清IgE和嗜酸性粒细胞增多症。最近，SPINK 5的单核苷酸多态性（SNP）被证明与特应性、特应性皮炎、哮喘和血清总IgE显著相关。为探讨SPINK 5基因在哮喘发病中的作用，对669例哮喘患者和711例健康对照者进行了病例对照研究。
方法
采用PCR-RFLP方法对启动子区的一个SNP（-206GA）和四个非同义SNP（1103 AG（Asn 368 Ser）、1156 GA（Asp 386 Asn）、1258 GA（Glu 420 Lys）和2475 GT（Glu 825 Asp））进行基因分型。此外，我们使用荧光素酶报告分析和电泳迁移率变动分析来分析-206GA的功能意义。
结果
我们发现SNP-206 GA的G等位基因与我们研究人群中哮喘易感性增加相关（p = 0.002，优势比1.34，95%置信区间1.11-1.60）。四个非同义SNPs中的任何一个与哮喘之间均无显著关联。在-206GA处的A等位基因具有比G等位基因显著更高的转录活性。电泳迁移率变动分析也显示核蛋白与A等位基因的结合效率显著高于G等位基因。
结论
我们的研究结果表明SPINK 5基因-206GA多态性与中国汉族人群哮喘易感性相关。
Background
Mutation in SPINK5 causes Netherton syndrome, a rare recessive skin disease that is accompanied by severe atopic manifestations including atopic dermatitis, allergic rhinitis, asthma, high serum IgE and hypereosinophilia. Recently, single nucleotide polymorphism (SNP) of the SPINK5 was shown to be significantly associated with atopy, atopic dermatitis, asthma, and total serum IgE. In order to determine the role of the SPINK5 in the development of asthma, a case-control study including 669 asthma patients and 711 healthy controls in Han Chinese was conducted.
Methods
Using PCR-RFLP assay, we genotyped one promoter SNP, -206GA, and four nonsynonymous SNPs, 1103AG (Asn368Ser), 1156GA (Asp386Asn), 1258GA (Glu420Lys), and 2475GT (Glu825Asp). Also, we analyzed the functional significance of -206GA using the luciferase reporter assay and electrophoresis mobility shift assay.
Results
we found that the G allele at SNP -206GA was associated with increased asthma susceptibility in our study population (p = 0.002, odds ratio 1.34, 95% confidence interval 1.11–1.60). There was no significant association between any of four nonsynonymous SNPs and asthma. The A allele at -206GA has a significantly higher transcriptional activity than the G allele. Electrophoresis mobility shift assay also showed a significantly higher binding efficiency of nuclear protein to the A allele compared with the G allele.
Conclusion
Our findings indicate that the -206GA polymorphism in the SPINK5 is associated with asthma susceptibility in a Chinese Han population.
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DOI：
10.1164/ajrccm.156.5.9702084
发表时间：
1997-11-01
影响因子：
24.7
作者：
Noguchi, E;Shibasaki, M;Hamaguchi, H
通讯作者：
Hamaguchi, H
影响因子：
30.8
作者：
Skol, AD;Scott, LJ;Boehnke, M
通讯作者：
Boehnke, M
影响因子：
158.5
作者：
POSTMA, DS;BLEECKER, ER;LEVITT, RC
通讯作者：
LEVITT, RC
影响因子：
10.3
作者：
Kato, A;Fukai, K;Ishii, M
通讯作者：
Ishii, M
影响因子：
4.4
作者：
Walley, AJ;Wiltshire, S;Cookson, WOCM
通讯作者：
Cookson, WOCM