Association between polymorphisms in ADAM33, CD14, and TLR4 with asthma in the Uygur population in China.

Association between polymorphisms in ADAM33, CD14, and TLR4 with asthma in the Uygur population in China.
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ADAM33、CD14 和 TLR4 多态性与中国维吾尔族人群哮喘的相关性。

DOI:
10.4238/2014.june.18.11
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发表时间:
2014-06
影响因子:
0.4
通讯作者:
Wen, H
Wen, H
中科院分区:
--
文献类型:
--
作者:
Yan, F;Zhang, J;Cui, S;Wen, H

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我们评估了编码解整合素和金属蛋白酶33(ADAM 33)、分化簇14(CD 14)和Toll样受体4(TLR 4)的基因单核苷酸多态性(SNPs)和单倍型与中国维吾尔族人群发生特定成人支气管哮喘表型的易感性之间的关系。对126例维吾尔族成人哮喘患者和126例正常对照进行了ADAM 33的5个SNP(T1、T2和V4)、CD 14的3个SNP(-1359G/T、-1145G/A和-159T/C)和TLR 4的2个SNP(-896A/G和-1196C/T)的基因分型。采用聚合酶链反应-限制性片段长度多态性分析检测基因多态性。使用直接DNA测序在我们样本的随机亚组中证实了基因分型结果。ADAM 33基因T1(TC)、T2(AG)、V4(GG)等位基因频率在患者组显著高于对照组(P<0.05)。T1(TC+CC)、T2(AG+AA)和V4(CG+GG)基因型显著增加哮喘的风险。在调整混杂因素后,这些关联更强,并且仍然显着。ADAM 33基因T1(TC)和V4(GG)基因型与哮喘患者FEV 1水平显著降低相关。Hap 3(CAC)和Hap 4(CAG)单倍型频率在患者组显著高于对照组(P<0.05)。我们的研究结果表明,T1,T2,和V4的ADAM 33基因多态性可能有助于对哮喘的易感性。中国维吾尔族人群中ADAM 33的特异性单倍型可能与哮喘易感性增高有关。
We evaluated the associations between single nucleotide polymorphisms (SNPs) and haplotypes of the genes encoding a disintegrin and metalloproteinase 33 (ADAM33), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) and the susceptibility of developing specific adult phenotypes of bronchial asthma in a Chinese Uygur population. Five SNPs of ADAM33 (T1, T2, and V4), 3 SNPs of CD14 (-1359G/T, -1145G/A, and -159T/C), and 2 SNPs of TLR4 (-896A/G and -1196C/T) were genotyped in a Chinese Uygur sample of 126 adult asthmatic patients and 126 control subjects. Gene polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism analysis. The genotyping results were confirmed in a random subgroup of our samples using direct DNA sequencing. The allele frequencies of ADAM33 T1 (TC), T2 (AG), and V4 (GG) were significantly higher in patients than in controls (P<0.05). The genotypes T1 (TC+CC), T2 (AG+AA), and V4 (CG+GG) significantly increased the risk of asthma. After adjusting for confounding factors, these associations were stronger and remained significant. The T1 (TC) and V4 (GG) genotypes in the ADAM33 gene were associated with significantly decreased FEV1 levels in patients with asthma. The haplotype frequencies of Hap3 (CAC) and Hap4 (CAG) were significantly higher in patients than in controls (P<0.05). Our results suggest that polymorphisms T1, T2, and V4 in ADAM33 may contribute to the susceptibility to asthma. Specific haplotypes of ADAM33 may contribute to a higher susceptibility to asthma in the Chinese Uygur population.
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