Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21.
Asthma affects nearly 14 million people worldwide and has been steadily increasing in frequency for the past 50 years. Although environmental factors clearly influence the onset, progression, and severity of this disease, family and twin studies indicate that genetic variation also influences susceptibility. Linkage of asthma and related phenotypes to chromosome 6p21 has been reported in seven genome screens, making it the most replicated region of the genome. However, because many genes with individually small effects are likely to contribute to risk, identification of asthma susceptibility loci has been challenging. In this study, we present evidence from four independent samples in support of HLA-G as a novel asthma and bronchial hyperresponsiveness susceptibility gene in the human leukocyte antigen region on chromosome 6p21, and we speculate that this gene might contribute to risk for other inflammatory diseases that show linkage to this region.
Nicolae
Dan
D
Department of Statistics, The University of Chicago, Chicago, IL, USA.
Cox
Nancy J
NJ
Lester
Lucille A
LA
Schneider
Daniel
D
Tan
Zheng
Z
Billstrand
Christine
C
Kuldanek
Susan
S
Donfack
Joseph
J
Kogut
Paul
P
Patel
Nina M
NM
Goodenbour
Jeffrey
J
Howard
Timothy
T
Wolf
Raoul
R
Koppelman
Gerard H
GH
White
Steven R
SR
Parry
Rodney
R
Postma
Dirkje S
DS
Meyers
Deborah
D
Bleecker
Eugene R
ER
Hunt
Joan S
JS
Solway
Julian
J
Ober
Carole
C
D000328:Adult; D001249:Asthma / Q000235:genetics*; D016535:Bronchial Hyperreactivity / Q000235:genetics; D002648:Child; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D008297:Male; D010641:Phenotype
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I