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过氧化物酶体增殖物激活受体α与糖尿病视网膜病变的关联,以及中国2型糖尿病患者中额外的基因-肥胖相互作用。

The association of peroxisome proliferator-activated receptor α with diabetic retinopathy, and additional gene-obesity interaction in Chinese type 2 diabetes mellitus patients.

作者信息

Qi Shounan, Wang Chenguang, Zhang Yan, Cheng Yan, Wang Shurong, Zhao Yixuan

机构信息

Eye Hospital, The second Hospital of Jilin University, Changchun 130041, China.

Eye Hospital, The second Hospital of Jilin University, Changchun 130041, China.

出版信息

Obes Res Clin Pract. 2016 Sep;10 Suppl 1:S103-S109. doi: 10.1016/j.orcp.2015.11.002. Epub 2015 Dec 3.

Abstract

AIMS

To investigate the impact of peroxisome proliferator-activated receptor α (PPAR α) SNPs and gene-obesity interaction on diabetic retinopathy (DR) susceptibility in a Chinese Han population.

METHODS

A total of 812 patients (373men, 439 women) with type 2 diabetes mellitus (T2DM), with a mean age of 53.3±14.0 years old, were selected, including 402 diabetic retinopathy patients and 410 controls. Three single nucleotide polymorphisms (SNPs) were selected for genotyping in the case-control study: rs4253778, rs135539 and rs1800206. Generalised multifactor dimensionality reduction (GMDR) and logistic regression model was used to examine the association and interaction between SNP and obesity on DR, odds ratio (OR) and 95% confident interval (95%CI) were calculated.

RESULTS

The carriers of homozygous mutant of rs1800206 SNP revealed decreased DR risk than those with wild-type homozygotes, OR (95%CI) was 0.78 (0.66-0.94). GMDR analysis indicated a significant two-locus model (p=0.0107) involving rs1800206 and abdominal obesity, indicating a potential interaction among rs1800206 and abdominal obesity. Overall, the two-locus models had a cross-validation consistency of 10 of 10, and had the testing accuracy of 60.72%. We also found that subjects with abdominal obesity and LV or VV genotype have lowest DR risk, compared to subjects with normal WC and LL genotype, OR (95%CI) was 0.39 (0.30-0.74), after covariates adjustment.

CONCLUSIONS

Our results support an important association between rs1800206 minor allele of PPAR α and DR, and the interaction analysis also shown a combined effect of Leu162 allele-abdominal obesity interaction on DR.

摘要

目的

探讨过氧化物酶体增殖物激活受体α(PPARα)单核苷酸多态性(SNP)及基因-肥胖相互作用对中国汉族人群糖尿病视网膜病变(DR)易感性的影响。

方法

选取812例2型糖尿病(T2DM)患者(男性373例,女性439例),平均年龄53.3±14.0岁,其中糖尿病视网膜病变患者402例,对照组410例。在病例对照研究中选择3个单核苷酸多态性(SNP)进行基因分型:rs4253778、rs135539和rs1800206。采用广义多因素降维法(GMDR)和逻辑回归模型检验SNP与肥胖对DR的关联及相互作用,计算比值比(OR)和95%置信区间(95%CI)。

结果

rs1800206 SNP纯合突变携带者的DR风险低于野生型纯合子,OR(95%CI)为0.78(0.66 - 0.94)。GMDR分析表明存在一个涉及rs1800206和腹型肥胖的显著两位点模型(p = 0.0107),提示rs1800206与腹型肥胖之间存在潜在相互作用。总体而言,两位点模型的交叉验证一致性为10/10,检验准确性为60.72%。我们还发现,与腰围正常且为LL基因型的受试者相比,腹型肥胖且为LV或VV基因型的受试者DR风险最低,经协变量调整后,OR(95%CI)为0.39(0.30 - 0.74)。

结论

我们的结果支持PPARα的rs1800206次要等位基因与DR之间存在重要关联,相互作用分析还显示Leu162等位基因-腹型肥胖相互作用对DR具有联合效应。

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