五聚環蛋白–3基因變異與糖尿病神經病變發展之關聯

糖尿病神經病變（diabetic neuropathy, DN）是一種常見的糖尿病併發症，包含多種類型的神經損傷，其病因在某種程度上歸因於多種遺傳參數的綜合表現。五聚環蛋白–3 (Pentraxin 3, PTX3) 最初被發現是抵抗傳染性病原體的關鍵因子，與發炎和組織再生密切相關。本研究評估了 730 例糖尿病神經病變病例和 861 例神經功能正常的糖尿病對照組中PTX3基因多型性與糖尿病神經病變的關聯。研究顯示，與帶有GG基因型的糖尿病患者相比，rs1840680 或 rs2120243基因多型性中帶有AA基因型的糖尿病患者更容易出現神經系統併發症。進一步研究顯示，這種與併發糖尿病神經病變的風險相關性在男性中被檢測到，但在女性中則沒有。另外數據也發現PTX3的另一組基因多型性 rs2305619與男性糖尿病神經病變風險相關，顯示PTX3基因多型性對糖尿病患者神經損傷具有性別性的影響。此外，我們發現rs1840680的AA基因型的糖尿病神經病變患者，尤其是男性，其 low-density lipoprotein膽固醇表現量高於GG基因型。總之，我們的數據顯示PTX3基因多型性與糖尿病患者的血脂異常和神經損傷之間存在性別特異性關聯。

Diabetic neuropathy (DN) is a prevalent complication of diabetes involving various types of nerve damage, and its etiology is to some extent attributed to a composite of genetic parameters. Pentraxin 3 (PTX3), initially discovered as a key player in defense against infectious pathogens, is crucial for inflammation and tissue regeneration. In this study, the link of PTX3 gene polymorphisms to DN was assessed between 730 DN cases and 861 diabetic controls with normal neurologic function. We demonstrated that diabetic subjects homozygous for AA genotype at rs1840680 or rs2120243 are more frequently to develop neurologic complications, as compared to diabetic subjects who are homozygous for GG genotype. Further stratification revealed that this correlation with DN risks was particularly detected in males but not in females. In addition, another SNP of PTX3 gene, rs2305619, was found in association with the risk for DN in males, indicating a gender-specific impact of PTX3 gene polymorphisms on damage to the nerves in diabetic patients. Furthermore, we found that DN patients homozygous for AA genotype of rs1840680, particularly the males, had higher levels of low-density lipoprotein-cholesterol than those homozygous for GG genotype. In conclusion, our data indicate an association of PTX3 gene polymorphisms with dyslipidemia and nerve damage in diabetic patients in a gender-specific manner.