Is hereditary hemochromatosis a balanced polymorphism: an analysis of family size among hemochromatosis heterozygotes.
BACKGROUND/AIMS: Hereditary hemochromatosis (HH) has a homozygote frequency of 0.5% and a heterozygote frequency of 13%, which suggests that hemochromatosis might be a balanced polymorphism. Evidence for this was sought by assessing reproductive success among hemochromatosis heterozygotes through determining their family size and incidence of miscarriage when compared to nongene carriers. METHODOLOGY: A cohort was defined in which the exposure variable was heterozygosity for hereditary hemochromatosis. Heterozygotes were identified by mailing individuals homozygous for hereditary hemochromatosis questionnaires concerning the number of siblings born alive and the number of miscarriages suffered by their mothers (predominantly heterozygotes, or HHH). Spouses of the hereditary hemochromatosis homozygotes were asked to complete accompanying questionnaires concerning their mothers (CONT). RESULTS: Five hundred and ninety-six responses were received from hereditary hemochromatosis homozygotes and 532 responses from spouses of the hereditary hemochromatosis homozygote respondents. The mothers of the hereditary hemochromatosis homozygote respondents had a mean family size of 3.699. The mothers of the unexposed spouse controls a mean family size of 3.639 (P = 0.66 by ANOVA). One hundred and twenty-three of the HHH mothers suffered a total of 201 miscarriages, whereas 94 of the CONT mothers suffered 147 miscarriages (P = 0.38 by ANOVA). CONCLUSIONS: In this cohort, no evidence among hemochromatosis heterozygotes of reproductive advantage and therefore heterozygous advantage by this mechanism was seen.