Asp327Asn polymorphism of sex hormone-binding globulin gene is associated with systemic lupus erythematosus incidence.
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.
Piotrowski
Piotr
P
Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznan, Poland.
Gasik
Robert
R
Lianeri
Margarita
M
Cieślak
Dorota
D
Wudarski
Mariusz
M
Hrycaj
Paweł
P
Łacki
Jan K
JK
Jagodziński
Paweł P
PP
D019943:Amino Acid Substitution / Q000235:genetics*; D001216:Asparagine / Q000235:genetics; D001224:Aspartic Acid / Q000235:genetics; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D015994:Incidence; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D011044:Poland / Q000453:epidemiology; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017697:Premenopause / Q000097:blood / Q000235:genetics; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*; D013739:Testosterone / Q000097:blood
D012738:Sex Hormone-Binding Globulin; D001224:Aspartic Acid; D013739:Testosterone; D004958:Estradiol; D001216:Asparagine