Estrogen receptor gene polymorphisms in Japanese patients with systemic sclerosis

Objective. To investigate whether single-nucleotide polymorphisms (SNPs) within the estrogen receptor (ER) α and β genes are associated with disease susceptibility and clinical presentation in Japanese patients with systemic sclerosis (SSc). Methods. Three SNPs, ERα PvuII T/C, ERα XbaI A/G, and ERβ 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 ERα 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 ERα 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). Conclusion. SNPs located within the ERα gene may contribute to disease susceptibility and to certain clinical manifestations of SSc patient.