Estrogen receptor gene polymorphisms in Japanese patients with systemic sclerosis.
OBJECTIVE
To investigate whether single-nucleotide polymorphisms (SNPs) within the estrogen receptor (ER) alpha and Beta genes are associated with disease susceptibility and clinical presentation in Japanese patients with systemic sclerosis (SSc).


METHODS
Three SNPs, ERalpha PvuII T/C, ERalpha XbaI A/G, and ERBeta RsaI G/A, were genotyped using polymerase-chain reaction combined with restriction fragment length polymorphisms in 103 patients with SSc and 56 race-matched healthy controls. The distribution of the individual ER SNPs in SSc patients with or without SSc-related organ involvement and serum antinuclear antibodies was determined.


RESULTS
The frequency of the ERalpha XbaI GG phenotype was significantly lower in SSc patients than in healthy controls (2% vs. 13%, p=0.005, odds ratio=0.14, 95%CI 0.03-0.69), and no significant association was detected for the other SNPs. Except in the case of heart involvement accompanying SSc, there was no significant association of the ER SNPs with SSc-related individual organ involvement or with antinuclear antibody profiles. Specifically, the ERalpha PvuII CC phenotype was significantly more frequent among patients with heart involvement compared with those without it (75% vs. 14%, p=0.0001, odds ratio=17.4, 95%CI 3.2-94.8).


CONCLUSIONS
SNPs located within the ERalpha gene may contribute to disease susceptibility and to certain clinical manifestations of SSc patients.
Hoshi
M
M
Department of Internal Medicine, Den-en Chofu Central Hospital, Tokyo, Japan.
Yasuoka
H
H
Kuwana
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012595:Scleroderma, Systemic / Q000235:genetics*; D055815:Young Adult
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta