Kim K M, Park S H, Kim J S, Lee W K, Cha S I, Kim C H, Kang Y M, Jung T H, Kim I S, Park J Y
Dept of Biochemistry, Kyungpook National University Hospital, Samduk 2a 50, Daegu, 700-412, Republic of Korea.
Eur Respir J. 2008 Jul;32(1):35-41. doi: 10.1183/09031936.00076207. Epub 2008 Apr 2.
A number of genome-wide linkage analyses have identified the 2q33.3-2q37.2 region as the most likely to contain the genes that contribute to the susceptibility to chronic obstructive pulmonary disease (COPD). It was hypothesised that the type IV collagen alpha3 (COL4A3) gene, which is one of the genes located in the 2q33.3-2q37.2 region, may act as a low-penetrance susceptibility gene for COPD. To test this hypothesis, the association of COL4A3 -1162T>C, IVS2+12C>A, P141L, G162E, H451R, P574L and *315C>A polymorphisms with the risk of COPD was investigated in a case-control study of 311 COPD patients and 386 controls. The presence of at least one 451R allele was associated with a significantly higher risk of COPD compared with the 451 H/H genotype (adjusted odds ratio 1.48, 95% confidence interval (1.03-2.14)). When the subjects were stratified according to age and COPD severity, the 451R allele was associated with a significantly higher risk of COPD only in younger individuals with severe COPD (3.02 (1.37-6.67)). In conclusion, these findings suggest that the type IV collagen alpha3 gene contributes to the genetic susceptibility to chronic obstructive pulmonary disease.
多项全基因组连锁分析已确定2q33.3 - 2q37.2区域最有可能包含导致慢性阻塞性肺疾病（COPD）易感性的基因。据推测，位于2q33.3 - 2q37.2区域的基因之一IV型胶原α3（COL4A3）基因可能作为COPD的低外显率易感基因。为验证这一假设，在一项针对311例COPD患者和386例对照的病例对照研究中，调查了COL4A3基因 - 1162T>C、IVS2 + 12C>A、P141L、G162E、H451R、P574L和*315C>A多态性与COPD风险的关联。与451 H/H基因型相比，至少存在一个451R等位基因与COPD风险显著升高相关（校正比值比1.48，95%置信区间（1.03 - 2.14））。当根据年龄和COPD严重程度对受试者进行分层时，451R等位基因仅在患有严重COPD的年轻个体中与COPD风险显著升高相关（3.02（1.37 - 6.67））。总之，这些发现表明IV型胶原α3基因对慢性阻塞性肺疾病的遗传易感性有影响。
