Piotrowski Piotr, Gasik Robert, Lianeri Margarita, Cieślak Dorota, Wudarski Mariusz, Hrycaj Paweł, Łacki Jan K, Jagodziński Paweł P
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznan, Poland.
Mol Biol Rep. 2010 Jan;37(1):235-9. doi: 10.1007/s11033-009-9639-7. Epub 2009 Aug 1.
Endogenous sex hormones have been observed to have a role in systemic lupus erythematosus (SLE) predisposition. Sex hormone-binding globulin (SHBG) regulates the bioavailability of sex hormones to target tissues. Therefore, we examined the distribution of the SHBG functional polymorphism Asp327Asn (rs6259) in SLE patients (n = 150) and controls (n = 150) in a Polish population. We found a contribution of the SHBG327Asn variant to the development of SLE. Women with the Asp/Asn and Asn/Asn genotypes displayed a 2.630-fold increased risk of SLE (95% CI = 1.561-4.433, P = 0.0003). SHBG has a much higher affinity for testosterone than estradiol, and the SHBG327Asn variant displays a reduction of estradiol clearance. Therefore we suggest that the opposing effects of estrogens and testosterone on the immune system and imbalance in the levels of these hormones in SLE patients can be enhanced by the SHBG327Asn protein variant.
内源性性激素已被观察到在系统性红斑狼疮（SLE）易感性中起作用。性激素结合球蛋白（SHBG）调节性激素对靶组织的生物利用度。因此，我们在波兰人群中检测了SLE患者（n = 150）和对照组（n = 150）中SHBG功能多态性Asp327Asn（rs6259）的分布。我们发现SHBG327Asn变体对SLE的发生有影响。Asp/Asn和Asn/Asn基因型的女性患SLE的风险增加了2.630倍（95% CI = 1.561 - 4.433，P = 0.0003）。SHBG对睾酮的亲和力比对雌二醇高得多，并且SHBG327Asn变体表现出雌二醇清除率降低。因此，我们认为雌激素和睾酮对免疫系统的相反作用以及SLE患者中这些激素水平的失衡可因SHBG327Asn蛋白变体而增强。
