连续尸检病例中 SERPINE2 基因的多态性与肺气肿有关。
Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases.
机构信息
Department of Molecular Epidemiology, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
出版信息
BMC Med Genet. 2010 Nov 10;11:159. doi: 10.1186/1471-2350-11-159.
BACKGROUND
The SERPINA1, SERPINA3, and SERPINE2 genes, which encode antiproteases, have been proposed to be susceptible genes for of chronic obstructive pulmonary disease (COPD) and related phenotypes. Whether they are associated with emphysema is not known.
METHODS
Twelve previously reported single nucleotide polymorphisms (SNPs) in SERPINA1 (rs8004738, rs17751769, rs709932, rs11832, rs1303, rs28929474, and rs17580), SERPINA3 (rs4934, rs17473, and rs1800463), and SERPINE2 (rs840088 and rs975278) were genotyped in samples obtained from 1,335 consecutive autopsies of elderly Japanese people. The association between these SNPs and the severity of emphysema, as assessed using macroscopic scores, was determined.
RESULTS
Emphysema of more than moderate degree was detected in 189 subjects (14.1%) and showed a significant gender difference (males, 20.5% and females, 7.0%; p < 0.0001). Among the 12 examined SNPs, only rs975278 in the SERPINE2 gene was positively associated with emphysema. Unlike the major alleles, homozygous minor alleles of rs975278 were associated with emphysema (odds ratio (OR) = 1.54; 95% confidence interval (CI) = 1.02-2.30; p = 0.037) and the association was very prominent in smokers (OR = 2.02; 95% CI = 1.29-3.15; p = 0.002).
CONCLUSIONS
SERPINE2 may be a risk factor for the development of emphysema and its association with emphysema may be stronger in smokers.
背景
编码蛋白酶抑制剂的 SERPINA1、SERPINA3 和 SERPINE2 基因被认为是慢性阻塞性肺疾病（COPD）和相关表型的易感基因。然而，它们是否与肺气肿有关尚不清楚。
方法
在 1335 例连续进行尸检的日本老年人样本中，对 SERPINA1（rs8004738、rs17751769、rs709932、rs11832、rs1303、rs28929474 和 rs17580）、SERPINA3（rs4934、rs17473 和 rs1800463）和 SERPINE2（rs840088 和 rs975278）的 12 个先前报道的单核苷酸多态性（SNP）进行了基因分型。通过宏观评分来评估这些 SNP 与肺气肿严重程度之间的关联。
结果
189 例（14.1%）患者存在中重度肺气肿，且存在显著的性别差异（男性为 20.5%，女性为 7.0%；p<0.0001）。在 12 个检测的 SNP 中，只有 SERPINE2 基因中的 rs975278 与肺气肿呈正相关。与主要等位基因不同，rs975278 的纯合次要等位基因与肺气肿相关（比值比（OR）=1.54；95%置信区间（CI）=1.02-2.30；p=0.037），并且这种关联在吸烟者中更为显著（OR=2.02；95%CI=1.29-3.15；p=0.002）。
结论
SERPINE2 可能是肺气肿发生的危险因素，其与肺气肿的关联在吸烟者中可能更强。
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