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Genome-wide Linkage Analysis of Pulmonary Function in Families of Children with Asthma in Costa Rica
  1. Craig P Hersh (craig.hersh{at}channing.harvard.edu)
  1. Brigham and Women's Hospital, United States
    1. Manuel E Soto-Quiros
    1. Hospital Nacional de Ninos, Costa Rica
      1. Lydiana Avila
      1. Hospital Nacional de Ninos, Costa Rica
        1. Stephen L Lake
        1. Brigham and Women's Hospital, United States
          1. Catherine Liang
          1. Brigham and Women's Hospital, United States
            1. Eduardo Fournier
            1. Hospital Nacional de Ninos, Costa Rica
              1. Mitzi Spesny
              1. Hospital Nacional de Ninos, Costa Rica
                1. Jody S Sylvia
                1. Brigham and Women's Hospital, United States
                  1. Ross Lazarus
                  1. Brigham and Women's Hospital, United States
                    1. Thomas Hudson
                    1. McGill University, Canada
                      1. Andrei Verner
                      1. McGill University, Canada
                        1. Barbara J Klanderman
                        1. Brigham and Women's Hospital, United States
                          1. Nelson B Freimer
                          1. University of California at Los Angeles, United States
                            1. Edwin K Silverman
                            1. Brigham and Women's Hospital, United States
                              1. Juan C Celedon (juan.celedon{at}channing.harvard.edu)
                              1. Brigham and Women's Hospital, United States

                                Abstract

                                Objective: Although asthma is highly prevalent among certain Hispanic subgroups, genetic determinants of asthma and asthma-related traits have not been conclusively identified in Hispanic populations. Therefore, we sought to identify genomic regions containing susceptibility loci for pulmonary function and bronchodilator response (BDR) in Costa Ricans.

                                Methods: Eight extended pedigrees were ascertained through schoolchildren with asthma in the Central Valley of Costa Rica. Short-tandem repeat (STR) markers were genotyped throughout the genome at an average spacing of 8.2 cM. Multipoint variance component linkage analyses of FEV1 and FEV1/FVC (both pre- and post-bronchodilator) and BDR were performed in these eight families (pre-bronchodilator spirometry, N=640; post-bronchodilator spirometry and BDR, N=624). Nine additional STR markers were genotyped on chromosome 7. Secondary analyses were repeated after stratification by cigarette smoking.

                                Results: Among all subjects, the highest logarithm of the odds of linkage (LOD) score for FEV1 (post-bronchodilator) was found on chromosome 7q34-35 (LOD=2.45, including the additional markers). The highest LOD scores for FEV1/FVC (pre-bronchodilator) and BDR were found on chromosomes 2q (LOD=1.53) and 9p (LOD=1.53), respectively. Among former and current smokers, there was near-significant evidence of linkage to FEV1/FVC (post-bronchodilator) on chromosome 5p (LOD=3.27) and suggestive evidence of linkage to FEV1 on chromosomes 3q (pre-bronchodilator, LOD=2.74) and 4q (post-bronchodilator, LOD=2.66).

                                Conclusions: In eight families of children with asthma in Costa Rica, there is suggestive evidence of linkage to FEV1 on chromosome 7q34-35. In these families, FEV1/FVC may be influenced by an interaction between cigarette smoking and a locus (loci) on chromosome 5p.

                                • bronchodilator agents
                                • pedigree
                                • smoking
                                • spirometry

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