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 IU/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.


CONCLUSIONS
These data are the first to suggest that common mitochondrial haplogroups influence the atopic diathesis.


CONCLUSIONS
These findings may provide a molecular explanation for the prominent influence of maternal history of atopy on the development of atopy in offspring.
Raby
Benjamin A
BA
Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115, USA. benjamin.raby@channing.harvard.edu
Klanderman
Barbara
B
Murphy
Amy
A
Mazza
Salvatore
S
Camargo
Carlos A
CA
Silverman
Edwin K
EK
Weiss
Scott T
ST
D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000453:epidemiology / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006238:Haploidy; D006579:Heterozygote; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood*; D015994:Incidence; D008928:Mitochondria / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012882:Skin Tests
D007073:Immunoglobulin E