Abstract：
BACKGROUND: Functional mutations or polymorphisms affecting forkhead box P3 (FOXP3) can lead to their abnormal FOXP3 gene expression and/or defective Treg cells generation, thus resulting in autoimmune disease and inflammatory disorders. FOXP3 also plays a key role in Type 2 diabetes mellitus (T2DM) and its complications, because the disease usually involves chronic low-grade inflammatory disorders and is associated with long-term immune system imbalance. This study aimed to investigate the association between FOXP3 polymorphisms and the susceptibility to T2DM and type 2 diabetes nephropathy (T2DN) within the Han Chinese populations.
METHODS: Polymorphisms in rs3761548C/A and rs2294021C/T were examined in 400 patients (which include an equal number of T2DM and T2DN groups) and 200 healthy controls using PCR-HRM and sequence analysis.
RESULTS: The genotype and allelic frequencies of the two single nucleotide polymorphisms (SNPs) were significantly different in T2DM and the progression of diabetes developing to T2DN. The further gender-based evaluation showed that in female subjects, rs3761548C/A was associated with an approximately 3-fold higher threat for T2DM and 4.5-fold for T2DN, while there was no noticeable association with rs2294021C/T; in males, the promoter polymorphism showed an increased predisposition of 5.4-fold and 3.4-fold predisposition to T2DM and T2DN, respectively, while rs2294021 polymorphism could impart a nearly 2-fold risk of developing T2DN. An additional analysis of combined genotypes (rs3761548 C/A-rs2294021C/T) revealed that CC-CC and CC-CT can be considered protective combinations in the predisposition of males with diabetes towards T2DN, while AA-CC and AA-TT have the opposite effect.
CONCLUSIONS: This study demonstrated the possible involvement of individual and combined genetic associations of rs3761548C/A and rs2294021C/T polymorphisms with the susceptibility to diabetes and diabetic nephropathy in the Han Chinese population, as well as gender bias.
METHODS: Polymorphisms in rs3761548C/A and rs2294021C/T were examined in 400 patients (which include an equal number of T2DM and T2DN groups) and 200 healthy controls using PCR-HRM and sequence analysis.
RESULTS: The genotype and allelic frequencies of the two single nucleotide polymorphisms (SNPs) were significantly different in T2DM and the progression of diabetes developing to T2DN. The further gender-based evaluation showed that in female subjects, rs3761548C/A was associated with an approximately 3-fold higher threat for T2DM and 4.5-fold for T2DN, while there was no noticeable association with rs2294021C/T; in males, the promoter polymorphism showed an increased predisposition of 5.4-fold and 3.4-fold predisposition to T2DM and T2DN, respectively, while rs2294021 polymorphism could impart a nearly 2-fold risk of developing T2DN. An additional analysis of combined genotypes (rs3761548 C/A-rs2294021C/T) revealed that CC-CC and CC-CT can be considered protective combinations in the predisposition of males with diabetes towards T2DN, while AA-CC and AA-TT have the opposite effect.
CONCLUSIONS: This study demonstrated the possible involvement of individual and combined genetic associations of rs3761548C/A and rs2294021C/T polymorphisms with the susceptibility to diabetes and diabetic nephropathy in the Han Chinese population, as well as gender bias.
摘要：
背景：影响叉头盒P3（FOXP3）的功能突变或多态性可导致其FOXP3基因表达异常和/或Treg细胞产生缺陷，从而导致自身免疫性疾病和炎症性疾病。FOXP3在2型糖尿病（T2DM）及其并发症中也起着关键作用，因为该疾病通常涉及慢性低度炎症性疾病，并与长期免疫系统失衡有关。本研究旨在探讨中国汉族人群中FOXP3基因多态性与T2DM和2型糖尿病肾病(T2DN)易感性的关系。
方法：使用PCR-HRM和序列分析在400例患者（包括相同数量的T2DM和T2DN组）和200例健康对照中检测rs3761548C/A和rs2294021C/T的多态性。
结果：两种单核苷酸多态性（SNP）的基因型和等位基因频率在T2DM和糖尿病发展为T2DN的过程中存在显着差异。进一步的基于性别的评估表明，在女性受试者中，rs3761548C/A与T2DM的威胁高约3倍和T2DN的威胁高约4.5倍相关，虽然与rs2294021C/T没有明显的关联；在男性中，启动子多态性显示T2DM和T2DN易感性增加5.4倍和3.4倍，分别,而rs2294021多态性可赋予发展为T2DN的近2倍风险。对组合基因型（rs3761548C/A-rs2294021C/T）的另一项分析显示，CC-CC和CC-CT可以被认为是男性糖尿病患者对T2DN的易感性的保护性组合，而AA-CC和AA-TT具有相反的效果。
结论：这项研究表明，在中国汉族人群中，rs3761548C/A和rs2294021C/T多态性与糖尿病和糖尿病肾病易感性的个体和组合遗传关联可能涉及。以及性别偏见。
方法：使用PCR-HRM和序列分析在400例患者（包括相同数量的T2DM和T2DN组）和200例健康对照中检测rs3761548C/A和rs2294021C/T的多态性。
结果：两种单核苷酸多态性（SNP）的基因型和等位基因频率在T2DM和糖尿病发展为T2DN的过程中存在显着差异。进一步的基于性别的评估表明，在女性受试者中，rs3761548C/A与T2DM的威胁高约3倍和T2DN的威胁高约4.5倍相关，虽然与rs2294021C/T没有明显的关联；在男性中，启动子多态性显示T2DM和T2DN易感性增加5.4倍和3.4倍，分别,而rs2294021多态性可赋予发展为T2DN的近2倍风险。对组合基因型（rs3761548C/A-rs2294021C/T）的另一项分析显示，CC-CC和CC-CT可以被认为是男性糖尿病患者对T2DN的易感性的保护性组合，而AA-CC和AA-TT具有相反的效果。
结论：这项研究表明，在中国汉族人群中，rs3761548C/A和rs2294021C/T多态性与糖尿病和糖尿病肾病易感性的个体和组合遗传关联可能涉及。以及性别偏见。
