The polymorphism of transforming growth factor-beta1 gene in Japanese patients with systemic sclerosis.
BACKGROUND
Transforming growth factor (TGF)-beta has been shown to be a potent stimulator of collagen production by fibroblasts, and could play a role in the pathogenesis of systemic sclerosis (SSc).


OBJECTIVE
To study the possible involvement of TGF-beta1 gene polymorphism in Japanese patients with SSc.


METHODS
Fifty-nine patients with SSc and 110 normal subjects were studied. Genomic DNA was extracted from skin tissues, and was amplified in a thermal cycler, generating a TGF-beta1 gene fragment with a size of 294 bp. The T to C transition at T869C (Leu10Pro) and the G to C transition at G915C (Arg25Pro) were identified by digestion with MspA1I and BglI, respectively.


RESULTS
At T869C (Leu10Pro), the frequency of the C allele in SSc (65.3%) was significantly higher than in normal controls (50.5%) (P < 0.01). SSc showed C/C allele 42.4%, C/T 45.8% and T/T 11.2%. Normal controls showed C/C allele 26.4%, C/T 48.2% and T/T 25.5%. The frequency of the C/C allele in SSc was significantly higher than in normal controls, in comparison with the T/T allele (P < 0.02), but no significant difference was found between the frequency of the C/C allele vs. the C/T allele. The frequency of the C/C allele showed no significant difference between diffuse and limited SSc. At G915C (Arg25Pro), all the normal controls and SSc patients showed only the G/G allele. These results are different from a previous study in which the frequency of the T/T allele was high in SSc at T869C (Leu10Pro).


CONCLUSIONS
This discrepancy may indicate that Japanese patients with SSc show a different genetic predisposition to TGF-beta1.
Ohtsuka
T
T
Department of Dermatology, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan. tohtsuka@dokkyomed.ac.jp
Yamakage
A
A
Yamazaki
S
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019943:Amino Acid Substitution; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012595:Scleroderma, Systemic / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1