Dept of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
Eur Respir J. 2011 Apr;37(4):791-9. doi: 10.1183/09031936.00026410. Epub 2010 Aug 6.
The surfactant protein (SP)-B gene may influence chronic obstructive pulmonary disease (COPD) and, thus, personalised medicine. We tested whether functional polymorphisms in SP-B (rs1130866 (1580T>C), rs2077079 (-18A>C) and rs3024791 (-384G>A)) associate with reduced lung function and risk of COPD in the general population. We genotyped 10,231 individuals from the general adult Danish population, and recorded spirometry and hospital admissions due to COPD. Because we previously found an association between the rare SP-B 121ins2 mutation and COPD among smokers, we stratified the analyses for smoking status. None of the individual SP-B genotypes or genotype combinations were associated with reduced forced expiratory volume in 1 s (FEV₁) % predicted, forced vital capacity (FVC) % pred and FEV₁/FVC overall or among smokers (p = 0.25-0.99). The odds ratio for spirometrically defined COPD did not differ from 1.0 for any of the SP-B genotypes or genotype combinations overall or among smokers (p = 0.17-0.78). Similar results were obtained for hospitalisation due to COPD (p = 0.07-0.93); we could exclude overall hazard ratios for heterozygotes of 1.18-1.21 and for homozygotes of 1.25-1.57 or larger for all three polymorphisms. In conclusion, the functional rs1130866, rs2077079 and rs3024791 polymorphisms in the SP-B gene are not associated with reduced lung function or risk of COPD, making it unlikely that these variants will be useful in personalised medicine.
表面活性蛋白 (SP)-B 基因可能会影响慢性阻塞性肺疾病 (COPD),进而影响个体化医学。我们测试了 SP-B 中的功能多态性 (rs1130866(1580T>C)、rs2077079(-18A>C)和 rs3024791(-384G>A)) 是否与一般人群中的肺功能降低和 COPD 风险相关。我们对来自丹麦普通成年人群的 10231 人进行了基因分型,并记录了肺活量测定和因 COPD 住院的情况。由于我们之前发现罕见的 SP-B 121ins2 突变与吸烟者中的 COPD 有关,因此我们对吸烟状况进行了分层分析。在所有人群中,单个 SP-B 基因型或基因型组合均与用力呼气量 1 秒 (FEV₁) 预计值、用力肺活量 (FVC) 预计值和 FEV₁/FVC 比值降低无关,吸烟者也如此 (p = 0.25-0.99)。任何 SP-B 基因型或基因型组合的比值比对于肺功能定义的 COPD 均无差异,无论在所有人群中还是在吸烟者中均如此 (p = 0.17-0.78)。因 COPD 住院的结果相似 (p = 0.07-0.93);我们可以排除所有三种多态性的杂合子总体比值比为 1.18-1.21,纯合子比值比为 1.25-1.57 或更大。总之,SP-B 基因中的功能性 rs1130866、rs2077079 和 rs3024791 多态性与肺功能降低或 COPD 风险无关,这些变体不太可能在个体化医学中有用。