Kisiel, B. M., Kosińska, J., Wierzbowska, M., Rutkowska-Sak, L., Musiej-Nowakowska, E., Wudarski, M., Olesinska, M., Krajewski, P., Łącki, J., Rell-Bakalarska, M., Jagodziński, P. P., Tłustochowicz, W., and Płoski, R.
Oestrogens acting via nuclear receptors (encoded by ESR1 or ESR2) are important for pathogenesis of systemic lupus erythematosus (SLE). rs2234693 and rs4986938 are two single nucleotide polymorphisms (SNPs) whose C and A variants increase transcription of ESR1 and ESR2, respectively. The T allele of rs2234693 was associated with early onset SLE, whereas the role of rs4986938 in SLE was not reported. Our aim was to examine the role of rs2234693 and rs4986938 in conferring susceptibility to juvenile and adult SLE (jSLE and aSLE). Genotype distribution of both SNPs was analysed in 84 jSLE, 112 aSLE patients and 1001 controls. Allele C of rs2234693 was associated with jSLE (OR = 1.87, p = 0.006, pcorrected = 0.02), whereas allele A of rs4986938 showed an association with aSLE (OR = 1.46, p = 0.008, pcorrected = 0.03). In jSLE, rs2234693 C had lower frequency in patients with central nervous system involvement (OR = 0.39, p = 0.005, pcorrected = 0.04) and showed a trend for increase among males, patients with renal involvement and those without DR2/3 (p < 0.05, pcorrected > 0.05). Whereas our results are consistent with a role of ESR1 variation in jSLE, more studies are needed since the direction of association was the opposite of that reported previously. The association between rs4986938 (ESR2) and aSLE is a novel finding, consistent with our recent report associating this variant with Graves’ disease. [ABSTRACT FROM AUTHOR]