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Sex Differences in Estrogen Receptor Gene Polymorphism and Its Association with Lupus Nephritis in Chinese

Background/Aims: Lupus nephritis (LN) is a clinical heterogeneous autoimmune disease and genetic factors contribute to the development of LN. One of the most striking characteristics in LN is the high prevalence among childbearing women, as well as that its clinical manifestation differs in women and men, suggesting the role of sex hormones in its pathogenesis. Methods: ThePvuII and XbaI restriction fragment length polymorphism (RFLP) of estrogen receptor (ER) gene were analyzed in 245 biopsy-proven LN patients (58 males and 187 females) and 172 normal controls (101 males and 71 females) by PCR-RFLP. The clinical and pathological features of 49 male and 152 female LN patients with different genotypes were analyzed. Results: It was found that genotype PpXx, ppxx and Ppxx were three major genotypes of ER gene in both of lupus patients and control groups. The distribution of ER gene polymorphism was quite different in lupus patients of different genders. The frequency of the PpXx genotype in male LN patients was significantly higher than both the gender matched normal controls (p < 0.05) and the female LN patients (p < 0.05), while no difference was shown in the frequency of PpXx genotype between female LN patients and gender matched controls. Interestingly, skin rashes and arthritis were found more common in the patients with PpXx genotype. The frequency of hematological abnormalities and hypertension were higher in patients with ppxx genotype (p < 0.05), while capillary thrombi and glomerular sclerosis were more frequently complicated in the patients with ppxx genotype. In addition, the renal vasculitis and interstitial injury were more frequent in those with Ppxx genotype (p < 0.01). Conclusion: The distribution of ER gene polymorphism in LN patients is distinct with different gender. The PpXxgenotype of ER gene may be associated with the susceptibility of SLE in male. ER gene polymorphism is probably one of the genetic factors contributing to the development of clinical heterogeneity and sexually dimorphic manifestations of LN.