TY - JOUR

T1 - Cystic fibrosis ΔF508 heterozygotes, smoking, and reproduction

T2 - studies of 9141 individuals from a general population sample

AU - Dahl, Morten

AU - Tybjaerg-Hansen, A

AU - Wittrup, H H

AU - Lange, P

AU - Nordestgaard, B G

N1 - Copyright 1998 Academic Press.

PY - 1998

Y1 - 1998

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 DeltaF508 heterozygotes; 250 carriers of this mutation were identified (2.7%). In the total sample DeltaF508 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 DeltaF508 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 DeltaF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking DeltaF508 heterozygotes experience a reproductive advantage while smoking DeltaF508 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 DeltaF508 heterozygotes; 250 carriers of this mutation were identified (2.7%). In the total sample DeltaF508 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 DeltaF508 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 DeltaF508 heterozygotes. However, the data cannot totally exclude the possibility that nonsmoking DeltaF508 heterozygotes experience a reproductive advantage while smoking DeltaF508 heterozygotes experience the opposite, a reproductive disadvantage. Accordingly, the data suggest a previously undocumented role of smoking on fecundity among cystic fibrosis heterozygotes.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Analysis of Variance

KW - Confounding Factors (Epidemiology)

KW - Cystic Fibrosis

KW - Cystic Fibrosis Transmembrane Conductance Regulator

KW - Denmark

KW - Family Characteristics

KW - Female

KW - Gene Frequency

KW - Heterozygote Detection

KW - Humans

KW - Male

KW - Middle Aged

KW - Mutation

KW - Reproduction

KW - Sex Factors

KW - Smoking

U2 - 10.1006/geno.1998.5272

DO - 10.1006/geno.1998.5272

M3 - Journal article

C2 - 9628826

VL - 50

SP - 89

EP - 96

JO - Genomics

JF - Genomics

SN - 0888-7543

IS - 1

ER -