Of Genes and Men: The Alternative View of Sex Differences in Cystic Fibrosis : Response to Creus et al.

Creus et al. (1) offer an intriguing hypothesis, namely that protective genes on the Y chromosome confer a survival advantage to men with cystic fibrosis. While there are aspects of this theory that are attractive, its does not explain the fact that in our series of >1,000 patients, survival was only decreased in women with both cystic fibrosis and diabetes (2). Survival in women without diabetes did not significantly differ from that of men with or without diabetes. While this does not preclude a genetic explanation, it suggests that excessive mortality in cystic fibrosis is related to the relationship between diabetes and sex rather than sex per se. Perhaps this is a direct negative interaction between diabetes and some factor associated with female physiology. Alternatively, there may be negative effects of diabetes that men but not women are able to overcome. These might be due to hormonal or other differences found in all men, but one could speculate that there may be protective genetic factors specific to men with cystic fibrosis. While diabetes affects men and women differently in the general population, the sex difference in cystic fibrosis is certainly more dramatic, and it is possible that genes on the Y chromosome may modify survival in men with cystic fibrosis–related diabetes.