Gu Harvest F, Alvarsson Alexandra, Efendic Suad, Brismar Kerstin
Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.
Gend Med. 2009 Dec;6(4):555-64. doi: 10.1016/j.genm.2009.11.001.
Sex-determining region Y-box 2 (SOX2) is a transcription factor that plays an important role in the induction of pluripotent stem cells from somatic cells. The SOX2 gene is located in chromosome 3q26.33, in the linkage region of diabetes and diabetic nephropathy (DN). Evidence indicates that SOX2 is expressed in the adult human pancreas.
This study investigated whether SOX2 is involved in the pathogenesis of diabetes and DN.
A genetic association study of the unique tag single nucleotide polymorphism (SNP) rs11915160 of the SOX2 gene was conducted in patients with type 1 diabetes mellitus (T1DM), with or without DN, who were identified from the Genetics of Kidneys in Diabetes (GoKinD) study.
In 1120 patients with T1DM (591 women, 529 men), SNP rs11915160 was found to be significantly associated with DN (odds ratio [OR] = 0.720; P = 0.038) and end-stage renal disease (OR = 0.686; P = 0.034) in women but not in men. Compared with male T1DM patients without DN, female T1DM patients without DN who carried the CC, CA, or AA genotype had reversed distribution patterns in HDL-C, creatinine, cystatin, and glycosylated hemoglobin. Among the female patients with DN, carriers of the AA genotype had lower creatinine and cystatin levels compared with carriers of the CC or CA genotype. Furthermore, this SOX2 genetic polymorphism and the adiponectin promoter polymorphism rs266729 had combined effects on DN.
The present study provides the first evidence that the SOX2 genetic polymorphism has gender-specific effects on DN, and also implies that transcription factors in pluripotency mechanisms may be involved in the pathogenesis of diabetes and DN.
性别决定区Y框蛋白2（SOX2）是一种转录因子，在从体细胞诱导多能干细胞过程中发挥重要作用。SOX2基因位于3号染色体q26.33，处于糖尿病和糖尿病肾病（DN）的连锁区域。有证据表明SOX2在成年人类胰腺中表达。
本研究调查SOX2是否参与糖尿病和DN的发病机制。
对1型糖尿病（T1DM）患者（无论有无DN）进行SOX2基因独特标签单核苷酸多态性（SNP）rs11915160的基因关联研究，这些患者来自糖尿病肾脏遗传学（GoKinD）研究。
在1120例T1DM患者（591例女性，529例男性）中，发现SNP rs11915160与女性的DN（优势比[OR]=0.720；P=0.038）和终末期肾病（OR=0.686；P=0.034）显著相关，而与男性无关。与无DN的男性T1DM患者相比，携带CC、CA或AA基因型的无DN的女性T1DM患者在高密度脂蛋白胆固醇、肌酐、胱抑素和糖化血红蛋白方面具有相反的分布模式。在患有DN的女性患者中，AA基因型携带者的肌酐和胱抑素水平低于CC或CA基因型携带者。此外，这种SOX2基因多态性与脂联素启动子多态性rs266729对DN有联合作用。
本研究提供了首个证据，表明SOX2基因多态性对DN有性别特异性影响，也意味着多能性机制中的转录因子可能参与糖尿病和DN的发病机制。
