Uncoupling Protein 2 and Peroxisome Proliferator-Activated Receptor γ Gene Polymorphisms in Association with Diabetes Susceptibility in Chinese Han Population with Variant Glucose Tolerance

Abstract

Objective To investigate the association of polymorphisms in uncoupling protein 2 (UCP2) and peroxisome proliferator-activated receptor (PPARγ) with glucolipid metabolism in Chinese Han population. Methods Five hundred eighty-nine subjects were divided into normal glucose tolerance (NGT) group (n = 198) and abnormal glucose tolerance group (n = 358). HbA1c, blood lipid profile, plasma glucose, and insulin were determined. Insulin sensitivity (HOMA-IR and Matsuda index (ISIM)) and insulin secretion indexes (HOMA-β, early and total phase disposition index) were evaluated. Eight potential functional SNPs in UCP2 and 7 in PPARγ were selected. SNPs were genotyped on Sequenom MassARRAY platform. Results The GG genotype of rs2920502 in PPARγ was associated with decreased risk of impaired glucose tolerance (G allele: OR: 0.818, 95%CI: 0.526–0.969, P = 0.042; GG: OR: 0.715, 95%CI: 0.527–0.97, P = 0.031). The TT genotype of rs3856806 in PPARγ was associated with increased risk of impaired glucose tolerance (T allele: OR: 1.46, 95%CI: 1.055–2.017, P = 0.022; TT: OR: 1.58, 95%CI: 1.104–2.761, P = 0.032). The GG genotype of rs2920502 in PPARγ had better blood glucose and increased insulin secretion and had lower HOMA-IR than GC/CC genotypes. Conclusion It probably could prevent insulin resistance in early stage by classifying the genotype of rs649446 and rs7109266 in UCP2. The GG genotype of rs2920502 in PPARγ had a decreased risk for diabetes. The TT genotype of rs3856806 in PPARγ had an increased risk for diabetes.

Polymorphism of Uncoupling Protein 2 (UCP2) Gene in Obes People with the Family History of Type 2 Diabetes Mellitus

“…Previous research with genotype analysis and further clinical features showed that subjects with the genotype TT rs649446 or subjects with AA rs7109266 genotype on UCP2 had higher HOMA-IR and HOMA-β, subjects with AA genotype rs7109266 also had a higher waist-hip ratio high, which suggests that subjects with TT genotype rs649446 or subjects with AA genotype rs7109266 are more prone to develop insulin resistance [18]. Previous studies have shown that human islet with GA genotype UCP2-866 polymorphism has decreased glucose-stimulated insulin secretion compared with GG.…”

UCP2 gene polymorphisms in obesity and diabetes, and the role of UCP2 in cancer

“…The I allele and DI genotype are more common in diabetic retinopathy among the Chinese population . The II and DI genotypes are associated with a higher risk of proliferative diabetic retinopathy and the DI genotype is associated with a higher risk of non‐proliferative diabetic retinopathy . In an Iranian study, the 45‐bp I/D polymorphism of the UCP2 gene is shown to be associated with the metabolic syndrome, which is being recognized as a risk factor for insulin resistance .…”

“…There are fewer reports on the 3 0 -UTR 45-bp I/D polymorphism in diabetes. The I allele and DI genotype are more common in diabetic retinopathy among the Chinese population [19,20]. The II and DI genotypes are associated with a higher risk of proliferative diabetic retinopathy and the DI genotype is associated with a higher risk of non-proliferative diabetic retinopathy [19,20].…”

“…Gene polymorphism, different from mutation, is an inherited variation in DNA sequence among populations, which may cause a change in the structure/function/activity of the gene product. UCP2 gene polymorphisms may play a pathological role in human diseases, such as cardiovascular disease , hypertension , diabetes , obesity and cancer .…”

Uncoupling Proteins as Therapeutic Targets for Neurodegenerative Diseases

“…In an attempt to obtain more direct evidence for the involvement of UCP2 in diabetic retinopathy, several groups have carried out GWAS studies and have identified a significant linkage between several UCP2 polymorphisms and the diabetic retinopathy phenotype [ 90 , 91 , 92 ]. Interestingly, the association was stronger with the more severe, proliferative forms of the disease.…”