The gene polymorphisms of UCP1 but not PPAR γ and TCF7L2 are associated with diabetic retinopathy in Chinese type 2 diabetes mellitus cases

Abstract

ABSTRACT.Purpose: This study was designed to investigate the association between the polymorphisms in three insulin resistance-related genes, uncoupling protein-1 (UCP1), peroxisome proliferator-activated receptor c (PPARc) and transcription factor 7-like 2 (TCF7L2) and the susceptibility to diabetic retinopathy (DR) in a Chinese type 2 diabetes mellitus (T2DM) cohort. Methods: A total of 792 patients with T2DM were enrolled and categorized into two groups: (1) the DR group consisted of 448 patients, which was further subclassified into a proliferative DR (PDR) group with 220 patients and a nonproliferative DR (NPDR) group with 228 patients; (2) the diabetes without retinopathy (DNR) group, comprised 344 patients who had no signs of DR. Single-nucleotide polymorphisms (SNPs), rs1800592 in the UCP1 gene, rs1801282, rs3856806 and rs1249719 in the PPARc gene and rs11196205 in the TCF7L2 gene were genotyped in this study. Results: For SNP rs1800592 of the UCP1 gene, the frequency of allele G and genotype GG was significantly higher in the PDR group than in the DNR group (allele OR: 1.32, 95% CI: 1.03-1.68, p = 0.03; genotype OR: 1.72, 95%CI: 1.06-2.79, p = 0.03). No evident association was found between the allele frequencies and genotype distributions of any individual SNP in the PPARc or TCF7L2 genes and DR, PDR or NPDR. Haplotype analyses of the PPARc gene did not provide any evidence for an association with DR, PDR or NPDR in this Chinese T2DM cohort. Conclusions: This study suggests that the SNP rs1800592 in the UCP1 gene is associated with increased risk of PDR in the Chinese T2DM population.

The rs6060566 of the reactive oxygen species modulator 1 (Romo‐1) gene affects Romo‐1 expression and the development of diabetic retinopathy in Caucasians with type 2 diabetes

“…Our study is the first one to demonstrate the rs6060566 of the Romo-1 gene to be associated with DR in subjects with T2DM, as no previous study has been reported to analyse the association of the Romo-1 polymorphism and any phenotype (in this case DR). Our results increase the knowledge of genetic risk factors for developing DR in T2DM (Bhargava et al 2014;Zhang et al 2015). It seems, however, that the retinopathy cases had a more severe form of T2DM in comparison with subjects without DR, that is cases had an earlier onset of diabetes, a longer duration of T2DM and a higher incidence of insulin therapy compared to the subjects without DR. Our findings are in accordance with UKPDS 22 and 50 studies that demonstrated the importance of an earlier onset of diabetes and a longer duration of diabetes (Davis et al 1997;Stratton et al 2001).…”

“…; Zhang et al. ). It seems, however, that the retinopathy cases had a more severe form of T2DM in comparison with subjects without DR, that is cases had an earlier onset of diabetes, a longer duration of T2DM and a higher incidence of insulin therapy compared to the subjects without DR. Our findings are in accordance with UKPDS 22 and 50 studies that demonstrated the importance of an earlier onset of diabetes and a longer duration of diabetes (Davis et al.…”

Haplotype-based interaction of the PPARGC1A and UCP1 genes is associated with impaired fasting glucose or type 2 diabetes mellitus

“…Nicoletti et al [16] analyzed the polymorphic locus of -3826 A>G (rs1800592) in the UCP1 gene and found that it increased the risk of T2DM in obese individuals. Besides that, a study by Zhang et al [31] showed that the allele G and genotype GG of the SNP rs1800592 in the UCP1 gene was associated with the increased risk of proliferative diabetic retinopathy (PDR) in the Chinese population with T2DM. Reasons for the inconsistent results may include: the occurrence and development of diseases are not only associated with the gene but may be modified by lifestyle and environment such as differences in nutritional and economic status.…”

Candidate gene studies of diabetic retinopathy in human

“…SNP rs1800592, which is located in the promoter of the UCP1 , has been shown to be associated with glucose homeostasis, adiposity and obesity, as well as changes in the body mass index (BMI) and body weight, resulting from metabolic disorders. UCP 1 has been implicated as a candidate marker for a risk factor of DR and the rs1800592 (c. A-3826G) polymorphism has been associated with PDR [75, 79]. Uncoupling protein 2 (UCP2) regulates production of reactive oxygen species (ROS) by mitochondria.…”