Association and preferential transmission of the CCR2V64I polymorphism with absence of asthma in high-risk families.
OBJECTIVE
To explore a possible association between the major functional CCR2V64I polymorphism and asthma and related phenotypes independent of atopy.


METHODS
We conducted this study in the Royal Aberdeen Children's Hospital, University of Aberdeen Medical School, United Kingdom from September 2004 to December 2006. One hundred and fifty-four unrelated nuclear families (598 individuals including children and parents) were identified from the local Grampian population. The major functional polymorphism CCR2V64I was analyzed for associations with asthma, lung function (forced expiratory volume% [FEV1%] of predicted), bronchial hyperresponsiveness (BHR) to methacholine, total serum-immunoglobulin E (s-IgE) and allergic sensitization (positive skin prick test to common allergens) in 154 asthmatic families.


RESULTS
Pedigree disequilibrium test and case control analyses showed that the CCR2V64I polymorphism was significantly associated with the absence of asthma FEV1%, predicted above the population median of 83%, but not with s-IgE levels or specific sensitization.


CONCLUSIONS
We identified associations between the V-64I CCR2 polymorphism and protection against asthma, higher FEV1, and absence of BHR in families at high risk of asthma and atopy, suggesting an important role for the CCR2 receptor in modulating airway inflammation independent of atopy.
Al-Abdulhadi
Saleh A
SA
Department of Child Health, Royal Aberdeen Children's Hospital, University of Aberdeen, Medical School, Aberdeen, Scotland, United Kingdom. dr.salehalabdulhadi@gmail.com
Al-Rabia
Mohammed W
MW
D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000235:genetics; D001985:Bronchial Provocation Tests; D002648:Child; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D008297:Male; D020641:Polymorphism, Single Nucleotide; D054390:Receptors, CCR2 / Q000235:genetics*; D055815:Young Adult
C515334:CCR2 protein, human; D054390:Receptors, CCR2; D007073:Immunoglobulin E