Association study of a polymorphism of the CTGF gene and susceptibility to systemic sclerosis in the Japanese population.
OBJECTIVE
To validate the association of a single nucleotide polymorphism (SNP) of the connective tissue growth factor gene (CTGF) with susceptibility to systemic sclerosis (SSc) in the Japanese population.


METHODS
395 Japanese patients with SSc, 115 patients with rheumatoid arthritis and 269 healthy Japanese volunteers were enrolled in the study. An SNP (rs6918698) at -945 bp from the start codon in the promoter region of the CTGF gene was determined by allelic discrimination with the use of a specific TaqMan probe.


RESULTS
The G allele showed a significantly higher frequency in patients with SSc than in controls (p<0.001; odds ratio 1.5; 95% confidence interval 1.2 to 1.9). In particular, the clinical subsets of SSc showed a more significant association between the G allele and diffuse cutaneous SSc (p<0.001) and the presence of interstitial lung disease (p<0.001), the presence of anti-topoisomerase I antibody (p<0.001) and anti-U1RNP antibody (p = 0.010). Association analyses using the genotype of the SNP yielded results similar to those of analyses using the allele.


CONCLUSIONS
This study confirms the association between an SNP in the CTGF gene and susceptibility to SSc, especially in the presence of diffuse cutaneous SSc, interstitial lung disease and anti-topoisomerase I antibody. The results strongly suggest that this SNP may be a powerful indicator of severe skin and lung involvement in patients with SSc.
Kawaguchi
Y
Y
Institute of Rheumatology, Tokyo Women's Medical University, Shinjuku-ku, Tokyo 162-0054, Japan. y-kawa@ior.twmu.ac.jp
Ota
Y
Y
Kawamoto
M
M
Ito
I
I
Tsuchiya
N
N
Sugiura
T
T
Katsumata
Y
Y
Soejima
M
M
Sato
S
S
Hasegawa
M
M
Fujimoto
M
M
Takehara
K
K
Kuwana
M
M
Yamanaka
H
H
Hara
M
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D001323:Autoantibodies / Q000032:analysis; D002648:Child; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012595:Scleroderma, Systemic / Q000150:complications / Q000235:genetics* / Q000276:immunology; D012867:Skin / Q000473:pathology; D055815:Young Adult
D001323:Autoantibodies; C526317:CCN2 protein, human; D055513:Connective Tissue Growth Factor