Genome-wide linkage analysis of pulmonary function in families of children with asthma in Costa Rica.
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 (FEV(1)) and FEV(1)/ 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 FEV(1) (post-bronchodilator) was found on chromosome 7q34-35 (LOD = 2.45, including the additional markers). The highest LOD scores for FEV(1)/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 FEV(1)/FVC (post-bronchodilator) on chromosome 5p (LOD = 3.27) and suggestive evidence of linkage to FEV(1) 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 FEV(1) on chromosome 7q34-35. In these families, FEV(1)/FVC may be influenced by an interaction between cigarette smoking and a locus (loci) on chromosome 5p.
Hersh
Craig P
CP
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Soto-Quirós
Manuel E
ME
Avila
Lydiana
L
Lake
Stephen L
SL
Liang
Catherine
C
Fournier
Eduardo
E
Spesny
Mitzi
M
Sylvia
Jody S
JS
Lazarus
Ross
R
Hudson
Thomas
T
Verner
Andrei
A
Klanderman
Barbara J
BJ
Freimer
Nelson B
NB
Silverman
Edwin K
EK
Celedón
Juan C
JC
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D001993:Bronchodilator Agents; D002648:Child; D003364:Costa Rica / Q000208:ethnology; D005541:Forced Expiratory Volume / Q000502:physiology; D008040:Genetic Linkage / Q000235:genetics*; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D012907:Smoking / Q000009:adverse effects / Q000503:physiopathology; D014797:Vital Capacity / Q000502:physiology
D001993:Bronchodilator Agents