A common mitochondrial haplogroup is associated with elevated total serum IgE levels

Background: Maternal history of asthma or atopy is among the most consistently reported risk factors for asthma and atopy in children, yet the molecular basis for this observation remains unclear. Mitochondria are inherited exclusively through the maternal line, raising the possibility that sequence variation in the mitochondrial genome contributes to the pathogenesis of asthma and atopy. Objective: We set out to determine whether common European mitochondrial haplogroups are associated with asthma-related atopic phenotypes. Methods: We studied 654 self-reported white children age 5 to 12 years with mild to moderate asthma participating in the Childhood Asthma Management Program. Eight haplogroup-tagging polymorphisms were genotyped with TaqMan probe hybridization assays, and mitochondrial haplogroup tests of association with asthma-related and atopy-related phenotypes were performed with haplo.stats. Results: We found significant evidence of mitochondrial haplogroup association with total serum IgE levels (global significance, P = .04), with carriers of European haplogroup U (frequency 11%) having higher total serum IgE levels (median level, 684 lU/L) compared with noncarriers (389 IU/L; P = .001). Haplogroup U carriers also had trends of greater skin prick test reactivity (P = .03) and higher frequency of atopic dermatitis (P = .07), although global haplogroup tests for these later 2 phenotypes were not significant at an alpha level of 0.05. Conclusion: These data are the first to suggest that common mitochondrial haplogroups influence the atopic diathesis. Clinical implications: These findings may provide a molecular explanation for the prominent influence of maternal history of atopy on the development of atopy in offspring.