COPDGene研究：早发型慢性阻塞性肺病与女性性别、母方因素及非裔美国人种有关

Rationale:

The characterization of young adults who develop late-onset diseases may augment the detection of novel genes and promote new pathogenic insights.

Methods:

We analyzed data from 2,500 individuals of African and European ancestry in the COPDGene Study. Subjects with severe, early-onset chronic obstructive pulmonary disease (COPD) (n=70, age<55yr, FEV1<50% predicted) were compared with older subjects with COPD (n=306, age>64yr, FEV1<50% predicted).

Measurements and Main Results:

Subjects with severe, early-onset COPD were predominantly females (66%), P="0".0004. Proportionally, early-onset COPD was seen in 42% (25 of 59) of African Americans versus 14% (45 of 317) of non-Hispanic whites, P<0.0001. Other risk factors included current smoking (56 vs. 17%, P<0.0001) and self-report of asthma (39 vs. 25%, P="0".008). Maternal smoking (70 vs. 44%, P="0".0001) and maternal COPD (23 vs. 12%, P="0".03) were reported more commonly in subjects with early-onset COPD. Multivariable regression analysis found association with African American race, odds ratio (OR), 7.5 (95% confidence interval [CI], 2.3–24; P="0".0007); maternal COPD, OR, 4.7 (95% CI, 1.3–17; P="0".02); female sex, OR, 3.1 (95% CI, 1.1–8.7; P="0".03); and each pack-year of smoking, OR, 0.98 (95% CI, 0.96–1.0; P="0".03).

Conclusions:

These observations support the hypothesis that severe, early-onset COPD is prevalent in females and is influenced by maternal factors. Future genetic studies should evaluate (1) gene-by-sex interactions to address sex-specific genetic contributions and (2) gene-by-race interactions.