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Of Genes and Men: The Alternative View of Sex Differences in Cystic Fibrosis

Response to Creus et al.

¹ U.K. Cystic Fibrosis Database, Division of Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, U.K
² Population Health Group, School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, U.K

Address correspondence to Erika J. Sims, PhD, University of East Anglia, Population Health Group, School of Medicine, Health Policy and Practice, Norwich, NR4 7TJ, U.K. E-mail: e.sims{at}uea.ac.uk

We thank Creus et al. (1) for their interesting comments on our proposal that female subjects with cystic fibrosis–related diabetes develop worse lung function compared with age- and genotype-matched male peers. They ask whether these differences are a result of "evolutionary, sex-specific selective pressures." They then make the assertion that cystic fibrosis heterozygosity must "simultaneously place an enormous selective pressure against men carrying these same ‘infertility’ alleles even in heterozygosity." The difficulty we face in accepting this notion of selective negative pressure on the Y chromosome is that most heterozygote males are perfectly fertile, but for reasons unknown, more males are diagnosed with cystic fibrosis than females (1.1 to 1.0). The latter ratio is higher than the accepted male preponderance at birth in the population as a whole (1.05 to 1.0), which is offset back toward unity by a higher male mortality in childhood (2).

We accept that it is not fully understood why some patients with apparently "severe genotypes" do not develop classical cystic fibrosis, although intronic/exonic boundary structure, modifier genes, and environmental factors have all been implicated (3). However, although Rodman et al. (3) reported that females outnumbered males by three to one in their late-diagnosed cohort, females formed a smaller proportion of their early-diagnosed cohort. But, Rodman et al.’s results contradict the recognized excess of female cystic fibrosis mortality (4). Indeed, we have recently submitted a manuscript responding to Rodman et al.’s findings and report that for a national population of 135 patients aged >40 years, comparable male-to-female ratios were found in pediatric- and adult-diagnosed cohorts (J.M., personal communication). The different findings between our work and that of Rodman et al. could indicate a possible unknown bias in a single-center approach (3).

Finally, Creus et al. (1) also suggest that "rather than decreased lung function and survival in women, we should view the published results as better survival and lung function in men." We suggest that the imminent imposition of neonatal screening across the U.K. and France provides an opportunity to test the ideas proposed by the correspondents, but we feel it is premature to envisage a change in the title of our report (5).

Acknowledgments

Supported by the Cystic Fibrosis Trust and the National Services Division of NHS (Scotland).

References

1. Creus M, Vogel W, Zoller H: Of genes and men: the alternative view of sex differences in cystic fibrosis (Letter). Diabetes Care 29:179–180, 2006[Free Full Text]
   
2. McCormick J, Green MW, Mehta G, Culross F, Mehta A: Demographics of the UK cystic fibrosis population: implications for neonatal screening. Eur J Hum Genet 10:583–590, 2002[Medline]
   
3. Rodman DM, Polis JM, Heltshe SL, Sontag MK, Chacon C, Rodman RV, Brayshaw SJ, Huitt GA, Iseman MD, Saavedra MT, Taussig LM, Wagener JS, Accurso FJ, Nick JA: Late diagnosis defines a unique population of long-term survivors of cystic fibrosis. Am J Respir Crit Care Med 171:621–626, 2005[Abstract/Free Full Text]
   
4. Rosenfeld M, Davis R, FitzSimmons S, Pepe M, Ramsey B: Gender gap in cystic fibrosis mortality. Am J Epidemiol 145:794–803, 1997[Abstract/Free Full Text]
   
5. Sims EJ, Green MW, Mehta A: Decreased lung function in female but not male subjects with established cystic fibrosis–related diabetes. Diabetes Care 28:1581–1587, 2005[Abstract/Free Full Text]
   

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This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sims, E. J. Articles by Mehta, A. Search for Related Content PubMed Articles by Sims, E. J. Articles by Mehta, A. Social Bookmarking                What's this?