Genetic association of the functional CDHR3 genotype with early-onset adult asthma in Japanese populations.
BACKGROUND
Recent studies have demonstrated that a coding SNP (rs6967330, Cys529→Tyr) in cadherin-related family member 3 (CDHR3), which was previously associated with wheezing illness and hospitalizations in infancy, could support efficient human rhinovirus C (RV-C) entry and replication. Here, we sought to examine the genetic contribution of this variant to the development of adult asthma.


METHODS
We performed a candidate gene case-control association study of 2 independent Japanese populations (a total of 3366 adults). The odds ratios (ORs) for association of the A allele at rs6967330 with adult asthma were calculated according to age at onset of asthma. In addition, the effect of the CDHR3 genotype on the development of specific asthma phenotypes was examined.


RESULTS
The A allele was associated with asthma (OR = 1.56; Mantel-Haenszel p = 0.0040) when the analysis was limited to patients with early-onset adult asthma. In addition, when the analysis was limited to atopic individuals, a stronger association of the CDHR3 variant with early-onset asthma was found, and interaction of the CDHR3 genotype with atopy was demonstrated. Finally, a significant association of this variant was specifically found with a phenotype of asthma characterized by atopy, early-onset, and lower lung function.


CONCLUSIONS
Our study supports the concept that the CDHR3 variant is an important susceptibility factor for severe adult asthma in individuals who develop the disease in early life. The interaction between the CDHR3 variant and atopy indicates that genetic predisposition to early respiratory viral infection is combined with atopy in promoting asthma.
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Jun
J
Kanazawa
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan. Electronic address: hmasuko@md.tsukuba.ac.jp.
Hironori
H
Masuko
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Yohei
Y
Yatagai
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Tohru
T
Sakamoto
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Hideyasu
H
Yamada
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Yoshiko
Y
Kaneko
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Haruna
H
Kitazawa
Tsukuba Medical Center, Tsukuba, Japan.
Hiroaki
H
Iijima
Tsukuba Medical Center, Tsukuba, Japan.
Takashi
T
Naito
National Hospital Organization, Ibarakihigashi National Hospital, Tokai, Japan.
Takefumi
T
Saito
Department of Medical Genetics, University of Tsukuba, Tsukuba, Japan.
Emiko
E
Noguchi
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Satoshi
S
Konno
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Masaharu
M
Nishimura
Laboratory for Respiratory and Allergic Diseases, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Tomomitsu
T
Hirota
Laboratory for Respiratory and Allergic Diseases, Center for Integrative Medical Sciences, Institute of Physical and Chemical Research (RIKEN), Kanagawa, Japan.
Mayumi
M
Tamari
Department of Pulmonary Medicine, University of Tsukuba, Tsukuba, Japan.
Nobuyuki
N
Hizawa
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011159:Population Surveillance; D012129:Respiratory Function Tests; D012307:Risk Factors; D055815:Young Adult
C586717:CDHR3 protein, human; D000070585:Cadherin Related Proteins; D015820:Cadherins; D008565:Membrane Proteins
Asthma phenotype; Cadherin-related family member 3 (CDHR3); Early-onset asthma; Genetics; Human rhinovirus C