Estrogen receptor alpha gene polymorphism and systemic lupus erythematosus: a possible risk?

Estrogens and their receptors may play a role in the pathogenesis of systemic lupus erythematosus. Genetic alterations in the exon 8-coding region of the estrogen receptor alpha alter the intracellular signalling of estrogens, leading in enhanced or diminished activity. We investigated whether genetic alterations in exon 8 of ERalpha gene are associated with the occurrence and clinical features of lupus disease. The coding region of ERalpha exon 8 was subjected to mutation analysis using the polymerase chain reaction, denaturing gradient gel electrophoresis and sequence analysis, using DNA isolated from whole blood of 36 female patients and 38 healthy females. Clinical and laboratory parameters were available from the patients' files. We identified the codon 594 polymorphism either in homozygous for the wild type gene (ACG/ACG) or heterozygous (ACG/ACA), both in patients and healthy females. Statistical analysis of the genotype and allele distribution revealed that there was a significant difference (chi2 test, P = 0.02 and P = 0.04, respectively) between patients and healthy women. Odds ratio estimate revealed that carriers of ACG/ACA genotype have three-fold higher risk of developing lupus disease (OR = 3.129, 95% CI 1.181-8.292). Moreover, in patients the heterozygous genotype was associated with rash, mouth ulcers and serositis (Fisher's exact test, P = 0.055, P = 0.083, P = 0.065, respectively). The heterozygous patients were associated significantly with an early age at disease onset (ANOVA test, P < 0.05). We conclude that estrogen receptor alpha codon 594 genotype may influence the development of systemic lupus erythematosus at a younger age, as well as a certain disease clinical pattern.