Association and preferential transmission of the CCR2V641 polymorphism with absence of asthma in high-risk families

Objectives: To explore a possible association between the major functional CCR2V641 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 Kingdon 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 above the population median of 83%, but not with s-IgE levels or specific sensitization. Conclusion: 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.