Li Tingting, Shi Yun, Yin Jieyun, Qin Qin, Wei Sheng, Nie Shaofa, Liu Li
Department of Epidemiology and Biostatistics, Key Laboratory of Environment and Health, Ministry of Education and Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Int Urol Nephrol. 2015 Jan;47(1):117-30. doi: 10.1007/s11255-014-0843-6. Epub 2014 Sep 28.
Hyperlipidaemia has been identified as a risk factor for diabetic nephropathy via exacerbation of glomerular injury through the activation of multiple signaling pathways. This study's aim is to assess the associations between polymorphisms of genes involved in lipid metabolism, such as apolipoprotein E (ApoE), peroxisome proliferator-activated receptor γ (PPARγ), acetyl-CoA carboxylase β (ACACB), and type 2 diabetic nephropathy (T2DN).
A search of the MEDLINE and Web of Science databases was used to identify relevant studies, and allele or genotype frequencies were pooled using fixed- or random-effects models.
Forty-five studies were included in this meta-analysis, consisting of 10,920 type 2 diabetic patients with nephropathy and 16,203 type 2 diabetic patients without nephropathy. The OR for ApoE ε2 versus ε3 was 1.49 (95% CI 1.13-1.95) in T2DN. The progression of T2DN was related to the presence of the ε2 allele and ε2 carrier with ORs of 1.72 (95% CI 1.10-2.69) and 1.78 (95% CI 1.18-2.69), respectively. The rs1801282 C>G variant in PPARγ presented a significant association with decreased T2DN risk, both in the G allele and GC/GG genotype with ORs of 0.77 (95% CI 0.68-0.87) and 0.79 (95% CI 0.69-0.92), respectively. The T allele in rs2268388 within ACACB showed an increased risk for T2DN, exhibiting an OR of 1.35 (95% CI 1.12-1.63).
Our meta-analysis supports that the ApoE ε2 allele and ACACB rs2268388 C>T might act as promotion factors of nephropathy in type 2 diabetes, whereas PPARγ rs1801282 C>G is a promising candidate genetic variation for reducing susceptibility to T2DN.
高脂血症已被确认为糖尿病肾病的一个危险因素，它通过激活多种信号通路加剧肾小球损伤。本研究的目的是评估参与脂质代谢的基因多态性，如载脂蛋白E（ApoE）、过氧化物酶体增殖物激活受体γ（PPARγ）、乙酰辅酶A羧化酶β（ACACB）与2型糖尿病肾病（T2DN）之间的关联。
通过检索MEDLINE和科学网数据库来识别相关研究，并使用固定效应或随机效应模型汇总等位基因或基因型频率。
本荟萃分析纳入了45项研究，包括10920例患有肾病的2型糖尿病患者和16203例无肾病的2型糖尿病患者。在T2DN中，ApoE ε2与ε3相比的比值比（OR）为1.49（95%可信区间[CI] 1.13 - 1.95）。T2DN的进展与ε2等位基因和ε2携带者的存在相关，OR分别为1.72（95% CI 1.10 - 2.69）和1.78（95% CI 1.18 - 2.69）。PPARγ中的rs1801282 C>G变异与降低T2DN风险显著相关，G等位基因和GC/GG基因型的OR分别为0.77（95% CI 0.68 - 0.87）和0.79（95% CI 0.69 - 0.92）。ACACB内rs2268388的T等位基因显示T2DN风险增加，OR为1.35（95% CI 1.12 - 1.63）。
我们的荟萃分析支持ApoE ε2等位基因和ACACB rs2268388 C>T可能是2型糖尿病肾病的促进因素，而PPARγ rs1801282 C>G是降低T2DN易感性的一个有前景的候选基因变异。
