TY - JOUR
T1 - Cystic fibrosis ΔF508 heterozygotes, smoking, and reproduction
T2 - Studies of 9141 individuals from a general population sample
AU - Dahl, Morten
AU - Tybjærg-Hansen, Anne
AU - Wittrup, Hans H.
AU - Lange, Peter
AU - Nordestgaard, Børge G.
PY - 1998/5/15
Y1 - 1998/5/15
N2 - Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is 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 9141 individuals was screened for cystic fibrosis ΔF508 heterozygotes; 250 carriers of this mutation were identified (2.7%). In the total sample ΔF508 heterozygotes did not have more children than noncarriers; however, smoking interacted with genotype in predicting number of children (ANOVA:P <0.001). Among nonsmokers, heterozygotes had more children than noncarriers (Wilcoxon: P = 0.03). Among smokers, the opposite was found: heterozygotes had fewer children than noncarriers (Wilcoxon: P = 0.001). These findings remained significant after allowing for gender and the potential confounders of age, income, and education. Finally, after allowing for these covariates, number of children in ΔF508 heterozygotes decreased with increasing extent of smoking (trend test: P = 0.003), while the opposite was true for noncarriers (trend test: P <0.001). In conclusion, overall these results do not support a reproductive advantage for cystic fibrosis ΔF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking ΔF508 heterozygotes experience a reproductive advantage while smoking ΔF508 heterozygotes experience the opposite, a reproductive disadvantage. Accordingly, the data suggest a previously undocumented role of smoking on fecundity among cystic fibrosis heterozygotes.
AB - Cystic fibrosis is the most common fatal autosomal recessive disease affecting Caucasian populations. It remains a puzzle how this disease is 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 9141 individuals was screened for cystic fibrosis ΔF508 heterozygotes; 250 carriers of this mutation were identified (2.7%). In the total sample ΔF508 heterozygotes did not have more children than noncarriers; however, smoking interacted with genotype in predicting number of children (ANOVA:P <0.001). Among nonsmokers, heterozygotes had more children than noncarriers (Wilcoxon: P = 0.03). Among smokers, the opposite was found: heterozygotes had fewer children than noncarriers (Wilcoxon: P = 0.001). These findings remained significant after allowing for gender and the potential confounders of age, income, and education. Finally, after allowing for these covariates, number of children in ΔF508 heterozygotes decreased with increasing extent of smoking (trend test: P = 0.003), while the opposite was true for noncarriers (trend test: P <0.001). In conclusion, overall these results do not support a reproductive advantage for cystic fibrosis ΔF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking ΔF508 heterozygotes experience a reproductive advantage while smoking ΔF508 heterozygotes experience the opposite, a reproductive disadvantage. Accordingly, the data suggest a previously undocumented role of smoking on fecundity among cystic fibrosis heterozygotes.
UR - http://www.scopus.com/inward/record.url?scp=0032524611&partnerID=8YFLogxK
U2 - 10.1006/geno.1998.5272
DO - 10.1006/geno.1998.5272
M3 - Article
C2 - 9628826
AN - SCOPUS:0032524611
VL - 50
SP - 89
EP - 96
JO - Genomics
JF - Genomics
SN - 0888-7543
IS - 1
ER -