Tripathi Priya, Awasthi Shally, Prasad Rajendra, Husain Nuzhat, Ganesh Subramaniam
Department of Pediatrics, Chhtrapati Shahuji Maharaj Medical University, Chowk, Lucknow 226 003, India.
J Genet. 2011 Aug;90(2):265-73. doi: 10.1007/s12041-011-0073-y.
ADAM33, a member of the ADAM (a disintegrin and metalloprotease) gene family, is an asthma susceptibility gene originally identified by positional cloning. In the present study, we investigated the possible association of five single-nucleotide polymorphisms (SNPs) in the ADAM33 (rs511898, rs528557, rs44707, rs597980 and rs2787094) with adult-onset asthma in an Indian population. The study included 175 patients with mild intermittent (n = 44), mild persistent (n = 108) or moderate persistent (n = 23) subgroups of asthma, and 253 nonasthmatic control individuals. SNPs were genotyped with the help of restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) method, and data were analysed using chi-square test and logistic regression model. Bonferroni's correction for multiple comparisons was applied for each hypothesis. Genotypes and allele frequencies of SNPs rs511898 and rs528557 were significantly associated with adult-onset asthma (P = 0.010-<0.001). A significant association of the homozygous mutant genotype and mutant alleles of SNPs rs2787094, rs44707 and rs597980 with the asthma was also observed (P = 0.020-<0.001). A positive association between asthma and haplotypes AGCCT, GGCCT, AGACT, GCAGT, GGACT, ACCCC and AGACC were also found (P = 0.036-<0.001, OR = 2.07-8.49). Haplotypes AGCGT, GCAGC, ACAGC, ACAGT, GGAGC and GGCGT appear to protect against asthma (P = 0.013-<0.0001, OR = 0.34-0.10). Our data suggest that ADAM33 gene polymorphisms serve as genetic risk factors for asthma in Indian adult population.
ADAM33是ADAM（一种去整合素和金属蛋白酶）基因家族的成员，是最初通过定位克隆鉴定出的哮喘易感基因。在本研究中，我们调查了ADAM33基因中的五个单核苷酸多态性（SNP，分别为rs511898、rs528557、rs44707、rs597980和rs2787094）与印度人群成年期哮喘的可能关联。该研究纳入了175例哮喘患者，分为轻度间歇性哮喘（n = 44）、轻度持续性哮喘（n = 108）或中度持续性哮喘（n = 23）亚组，以及253名非哮喘对照个体。借助限制性片段长度多态性聚合酶链反应（RFLP-PCR）方法对SNP进行基因分型，并使用卡方检验和逻辑回归模型分析数据。对每个假设均应用Bonferroni多重比较校正。SNP rs511898和rs528557的基因型和等位基因频率与成年期哮喘显著相关（P = 0.010 - <0.001）。还观察到SNP rs2787094、rs44707和rs597980的纯合突变基因型和突变等位基因与哮喘存在显著关联（P = 0.020 - <0.001）。还发现哮喘与单倍型AGCCT、GGCCT、AGACT、GCAGT、GGACT、ACCCC和AGACC之间存在正相关（P = 0.036 - <0.001，OR = 2.07 - 8.49）。单倍型AGCGT、GCAGC、ACAGC、ACAGT、GGAGC和GGCGT似乎对哮喘有保护作用（P = 0.013 - <0.0001，OR = 0.34 - 0.10）。我们的数据表明，ADAM33基因多态性是印度成年人群哮喘的遗传危险因素。
