Abstract

Various studies in mice have found support for the hypothesis that heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations have an increased resistance to fatal infection compared to both homozygous mutation carriers and non-carriers, while in humans such evidence is scarce. In this study, we assessed the CFTR heterozygotes survival advantage hypothesis in a contemporary rural population that lives under adverse environmental conditions in the Upper-East region of Ghana. We genotyped 30 SNPs throughout the CFTR gene in 4,230 participants and tested their influence on survival and on body composition in the population at large. With a sliding-window haplotype analysis, we identified a set of six common haplotypes that influenced survival probabilities (global p = 6.00 x 10(-05)). Individual haplotype analyses revealed two haplotypes of specific interest. One of these haplotypes was enriched (p = 0.003), whereas the other was depleted (p = 0.041) among people of old age (> or = 65 years) compared to young study participants (< or = 5 years). In addition, children (n = 474) carrying the latter haplotype had lower body weight (p (trend) = 0.020) and height (p (trend) = 0.010) compared to non-carriers. For all these analyses, similar associations for heterozygous and homozygous CFTR haplotype carriers were observed, revealing an additive effect of haplotype alleles. In conclusion, we identified common haplotypes in the CFTR gene that influence survival and body composition in the population at large with no evidence for heterozygote advantage.