南方医科大学学报 ›› 2015, Vol. 35 ›› Issue (07): 1019-.

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2型糖尿病患者PEDF基因启动子区多态性与非酒精性脂肪肝病的相关性

黄文森,施亚雄,杨鑫娜,林莞蓉   

  • 出版日期:2015-07-20 发布日期:2015-07-20

Association between polymorphisms in pigment epithelium-derived factor gene
promoter region and non-alcoholic fatty liver disease in type 2 diabetes mellitus

  • Online:2015-07-20 Published:2015-07-20

摘要: 目的探讨福建地区汉族2 型糖尿病患者血清色素上皮衍生因子水平及色素上皮衍生因子基因启动子区-358 位点单
核苷酸多态性与非酒精性脂肪肝病的关系。方法选择2 型糖尿病患者共452 例,按有无合并非酒精性脂肪肝病分为性别、
年龄比例相近的DM1 组(合并非酒精性脂肪肝病)282 例,DM2 组(不合并非酒精性脂肪肝病)170 例,采用聚合酶链反应
——限制性片段长度多态性(PCR-RFLP)技术检测色素上皮衍生因子基因启动子区-358 位点多态性,同时检测血清色素上
皮衍生因子水平及空腹血糖、空腹胰岛素、糖化血红蛋白等指标。结果DM1 组的血清色素上皮衍生因子水平高于DM2
组,差异有统计学意义(P<0.05);以非酒精性脂肪肝病为因变量的二分类非条件Logistic 回归分析中,结果显示血清色素上
皮衍生因子作为独立影响因素影响2 型糖尿病患者非酒精性脂肪肝病的发生;色素上皮衍生因子基因启动子区
SNP-358G→A的基因型(GG型、GA型和AA型)和等位基因(G/A)在DM1、DM2 两组间的分布存在差异,有统计学意义(P<
0.05);2 型糖尿病患者-358 位点GA基因型出现非酒精性脂肪肝病的风险是GG基因型的2.032 倍,GA+AA基因型出现非酒
精性脂肪肝病的风险是GG基因型的2.068 倍,差异有统计学意义(P<0.05)。结论血清色素上皮衍生因子水平是2 型糖尿
病患者发生非酒精性脂肪肝病的独立影响因素,血清色素上皮衍生因子水平的升高为胰岛素抵抗的反馈表现,可改善胰岛
素抵抗,保护胰岛素敏感性。2 型糖尿病患者的色素上皮衍生因子基因启动子区-358G→A多态性与非酒精性脂肪肝病有
关,携带A等位基因可能增加非酒精性脂肪肝病的易感性。

Abstract: Objective To investigate the association of serum pigment epithelium-derived factor (PEDF) level and
polymorphisms in PEDF gene promoter region -358G→A with non-alcoholic fatty liver disease (NAFLD) in patients with type
2 diabetes mellitus (T2DM) of Han Nationality in Fujian Province. Methods A total of 282 T2DM patients with NAFLD (DM1
group) and 170 age- and gender-matched T2DM patients without NAFLD (DM2 group) were examined for PEDF gene
SNP-358G→A polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Serum pigment epithelium-derived factor(PEDF) level, fasting plasma glucose (FPG), fasting insulin (FINS) and glycosylated
hemoglobin (HbA1c) were also measured. Results The patients in DM1 group showed a significantly higher mean level of
serum PEDF than those in DM2 group (P<0.05). Logistic regression analysis revealed that PEDF level was an independent risk
factor for NAFLD in T2DM. The frequencies of PEDF gene -358G→A genotypes (GG, GA, and AA) and alleles (G/A) differed
significanly between DM1 and DM2 groups (P<0.05). In terms of PEDF gene SNP -358G→A alleles, the GA genotype carriers
had a 2.032 times higher risk of developing NAFLD compared with the GG genotype carriers, and the risk increased to 2.068
times in the carriers of the A allele (GA and AA genotypes; P<0.05). Conclusion Serum PEDF level is an independent risk factor
of NAFLD in T2DM. Elevated serum PEDF level is a protective factor against insulin resistance. In T2DM patients, PEDF gene
promoter region -358G→A polymorphism is associated with NAFLD, and the A allele contributes to an increased risk of
NAFLD.