CYSTIC-FIBROSIS DELTA-F508 HETEROZYGOTES, SMOKING, AND REPRODUCTION -STUDIES OF 9141 INDIVIDUALS FROM A GENERAL-POPULATION SAMPLE

Cystic fibrosis is the most common fatal autosomal recessive disease a ffecting Caucasian populations. It remains a puzzle how this disease i s maintained at such a remarkably high incidence, however, it could be due to a reproductive advantage in cystic fibrosis heterozygotes. We tested this hypothesis. An adult Danish general population sample of 9 141 individuals was screened for cystic fibrosis Delta F508 heterozygo tes; 250 carriers of this mutation were identified (2.7%). In the tota l sample Delta F508 heterozygotes did not have more children than nonc arriers; however, smoking interacted with genotype in predicting numbe r of children (ANOVA: P < 0.001). Among nonsmokers, heterozygotes had more children than noncarriers (Wilcoxon: P = 0.03). Among smokers, th e opposite was found: heterozygotes had fewer children than noncarrier s (Wilcoxon: P = 0.001). These findings remained significant after all owing for gender and the potential confounders of age, income, and edu cation. Finally, after allowing for these covariates, number of childr en in Delta F508 heterozygotes decreased with increasing extent of smo king (trend test: P = 0.003), while the opposite was true for noncarri ers (trend test: P < 0.001). In conclusion, overall these results do n ot support a reproductive advantage for cystic fibrosis Delta F508 het erozygotes. However, the data cannot totally exclude the possibility t hat nonsmoking Delta F508 heterozygotes experience a reproductive adva ntage while smoking Delta F508 heterozygotes experience the opposite, a reproductive disadvantage. Accordingly, the data suggest a previousl y undocumented role of smoking on fecundity among cystic fibrosis hete rozygotes. (C) 1998 Academic Press.