Significant linkage to airway responsiveness on chromosome 12q24 in families of children with asthma in Costa Rica.
Although asthma is a major public health problem in certain Hispanic subgroups in the United States and Latin America, only one genome scan for asthma has included Hispanic individuals. Because of small sample size, that study had limited statistical power to detect linkage to asthma and its intermediate phenotypes in Hispanic participants. To identify genomic regions that contain susceptibility genes for asthma and airway responsiveness in an isolated Hispanic population living in the Central Valley of Costa Rica, we conducted a genome-wide linkage analysis of asthma (n = 638) and airway responsiveness (n = 488) in members of eight large pedigrees of Costa Rican children with asthma. Nonparametric multipoint linkage analysis of asthma was conducted by the NPL-PAIR allele-sharing statistic, and variance component models were used for the multipoint linkage analysis of airway responsiveness as a quantitative phenotype. All linkage analyses were repeated after exclusion of the phenotypic data of former and current smokers. Chromosome 12q showed some evidence of linkage to asthma, particularly in nonsmokers (P < 0.01). Among nonsmokers, there was suggestive evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 2.33 at 146 cM). After genotyping 18 additional short-tandem repeat markers on chromosome 12q, there was significant evidence of linkage to airway responsiveness on chromosome 12q24.31 (LOD = 3.79 at 144 cM), with a relatively narrow 1.5-LOD unit support interval for the observed linkage peak (142-147 cM). Our results suggest that chromosome 12q24.31 contains a locus (or loci) that influence a critical intermediate phenotype of asthma (airway responsiveness) in Costa Ricans.
Celedón
Juan C
JC
Channing Laboratory, Department of Medicine and Respiratory Disorders Program, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA. juan.celedon@channing.harvard.edu
Soto-Quiros
Manuel E
ME
Avila
Lydiana
L
Lake
Stephen L
SL
Liang
Catherine
C
Fournier
Eduardo
E
Spesny
Mitzi
M
Hersh
Craig P
CP
Sylvia
Jody S
JS
Hudson
Thomas J
TJ
Verner
Andrei
A
Klanderman
Barbara J
BJ
Freimer
Nelson B
NB
Silverman
Edwin K
EK
Weiss
Scott T
ST
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D016085:Bronchoconstrictor Agents / Q000627:therapeutic use; D002648:Child; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D003364:Costa Rica; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D006801:Humans; D008126:Lod Score; D008297:Male; D016210:Methacholine Chloride / Q000627:therapeutic use; D018895:Microsatellite Repeats; D008875:Middle Aged; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology*
D016085:Bronchoconstrictor Agents; D016210:Methacholine Chloride