Association study of the C3 gene with adult and childhood asthma.
Bronchial asthma (BA) is a multifactorial disorder, the development of which is affected by both environmental and genetic factors. The complement system plays an important role in immunological response against invading microorganisms. It has been shown that complement-C3-deficient mice have reduced inflammation of asthmatic airways. Previously, we reported the association of four single nuclear proteins (SNPs) in the exons of the C3 gene with childhood and adult BA. The C3 gene, however, is a large gene, and functional SNPs associated with susceptibility to BA have not yet been identified. We analyzed 26 SNPs in the C3 gene and its promoter region to narrow down the regions showing association with childhood and adult BA. Childhood and adult atopic BA patients and healthy child and adult controls were recruited from urban cities in Japan and genotyped. In SNP analysis, an SNP (SNP24, rs11569562) located in intron 31 of the C3 gene was associated with adult BA [corrected P (Pcor) = 0.030]. In linkage disequilibrium (LD) block 4 spanning exons 24-41, the frequency of the CCC haplotype in adult BA was significantly higher than that in adult controls (Pcor = 0.038). Neither the SNP nor the haplotype showing association with adult BA demonstrated a significant association with serum total immunoglobulin E (IgE) level in BA patients and controls. Our results suggest that LD block 4 confers susceptibility to adult BA with mechanisms relevant to the effector phase of allergic inflammation.
Department of Public Health, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Hiroki
H
Inoue
Department of Public Health, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Yoichi
Y
Mashimo
Department of Public Health, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Makiko
M
Funamizu
Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Naoki
N
Shimojo
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Koichi
K
Hasegawa
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Tomomitsu
T
Hirota
Department of Pediatrics, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.
Satoru
S
Doi
Department of Pediatrics, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Habikino, Japan.
Makoto
M
Kameda
Miyatake Asthma Clinic, Osaka, Japan.
Akihiko
A
Miyatake
Department of Pediatrics, Graduate School of Medicine, Chiba University, Chiba, Japan.
Yoichi
Y
Kohno
Department of Otolaryngology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Yoshitaka
Y
Okamoto
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Mayumi
M
Tamari
Department of Public Health, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Akira
A
Hata
Department of Public Health, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan. ysuzuki@faculty.chiba-u.jp.
Yoichi
Y
Suzuki
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D002417:Cattle; D002648:Child; D002675:Child, Preschool; D003176:Complement C3 / Q000235:genetics*; D004285:Dogs; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
C038245:C3 protein, human; D003176:Complement C3