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Polymorphism in the Surfactant Protein-B Gene, Gender, and the Risk of Direct Pulmonary Injury and ARDS^*

^* From the Pulmonary and Critical Care Unit (Drs. Gong, Thompson, and Christiani), Department of Medicine, Massachusetts General Hospital, Harvard Medical School; and the Environmental Health Department (Drs. Wei, Xu, and Miller), Harvard School of Public Health, Boston, MA.

Correspondence to: David C. Christiani, MD, FCCP, Harvard School of Public Health, 665 Huntington Ave, Boston, MA 02115; e-mail: dchris{at}hohp.harvard.edu

Study objective: Major risk factors for ARDS have been identified. However, only a minority of patients with such risks develops ARDS. It is likely that, given the same type and degree of insult, there are heritable determinants of susceptibility to ARDS. To investigate the possibility of variable genetic susceptibility to ARDS, we examined the association between ARDS and a polymorphism in intron 4 of the surfactant protein-B (SP-B) gene.

Design: Nested case-control study conducted from September 1999 to March 2001.

Setting: Four adult medical and surgical ICUs at a tertiary academic center.

Patients: One hundred eighty-nine patients meeting study criteria for a defined risk factor for ARDS were enrolled and prospectively followed.

Measurements and results: Seventy-two patients (38%) developed ARDS. After stratification by gender and adjustment for potential confounders, there was a significantly increased odds for women with the variant SP-B gene to develop ARDS compared to women homozygous for the wild-type allele (odds ratio [OR], 4.5; 95% confidence interval [CI], 1.1 to 18.8; p = 0.03). Women with the variant SP-B polymorphism also had significantly increased odds of having a direct pulmonary injury such as aspiration or pneumonia as a risk factor for ARDS as opposed to an indirect pulmonary risk for ARDS (OR, 4.6; 95% CI, 1.1 to 19.9; p = 0.04). No such association with ARDS or direct pulmonary injury was found for men.

Conclusion: The variant polymorphism of the SP-B gene is associated with ARDS and with direct pulmonary injury in women, but not in men. Further study is needed to confirm the association between the variant SP-B gene, and gender, ARDS, and direct pulmonary injury.

Key Words: ARDS • genetic susceptibility • surfactant

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