ASTHMA

Genome-wide linkage analysis of pulmonary function in families of children with asthma in Costa Rica

Craig P Hersh¹, Manuel E Soto-Quirós², Lydiana Avila², Stephen L Lake¹, Catherine Liang¹, Eduardo Fournier², Mitzi Spesny², Jody S Sylvia¹, Ross Lazarus¹, Thomas Hudson³, Andrei Verner³, Barbara J Klanderman¹, Nelson B Freimer⁴, Edwin K Silverman¹, Juan C Celedón¹

¹ Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
² Division of Pediatric Pulmonology, Hospital Nacional de Niños, San José, Costa Rica
³ McGill University and Genome Quebec Innovation Centre, Montreal, Canada
⁴ Department of Psychiatry, University of California at Los Angeles, Los Angeles, California

Correspondence to:
Dr J C Celedón
Channing Laboratory, Brigham and Women’s Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; juan.celedon{at}channing.harvard.edu

Background: 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. A study was undertaken to identify genomic regions containing susceptibility loci for pulmonary function and bronchodilator responsiveness (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 forced expiratory volume in 1 second (FEV₁) and FEV₁/ forced vital capacity (FVC; both pre-bronchodilator 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.

Abbreviations: BDR, bronchodilator responsiveness; COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; LOD, logarithm of the odds of linkage; SOLAR, Sequential Oligogenic Linkage Analysis Routines; STR, short tandem repeat

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