title: Combined analysis of polymorphism variants in hMTH1, hOGG1 and MUTYH genes on the risk of type 2 diabetes in the Chinese population.
abstract: Reactive oxygen species are considered to play a role in the development of type 2 diabetes mellitus (T2DM) and its complications. 8-Oxoguanine, which is one of the major oxidation base lesions produced by reactive oxygen species, may cause G:C to T:A transversion mutations because it can mispair with adenine. hMTH1 (human mutT homolog 1), hOGG1 (human 8-oxoguanine glycosylase 1) and MUTYH (human mutY homolog) genes constitute the 8-oxoG repair pathway. In this study, we screened for the polymorphism variants Val83Met (c.247G>A, rs4866) in hMTH1; c.-53G>C (rs56387615), c.-23A>G (rs1801129) and c.-18G>T (rs1801126) in the 5'-UTR of hOGG1; and AluYb8 insertion in MUTYH (AluYb8MUTYH, rs10527342) and investigated their synergistic effect on the risk of T2DM in the Chinese population. The genotypes were determined by electrophoresis, a high-resolution melting technique and sequencing of PCR products. Our results showed that the c.247G>A variant in the hMTH1 gene increased the risk of T2DM in >55 years of age groups (OR=1.579; 95%CI: 1.029-2.421). The set of c.-53G>C, c.-23A>G and c.-18G>T variants detected in the 5'-UTR of the hOGG1 gene and the AluYb8 insertion in the MUTYH gene were each associated with an increased risk of T2DM (OR=1.507, 95%CI: 1.122-2.024; OR=1.229, 95%CI: 1.030-1.466, respectively). Combined analysis of the variations among the three genes suggested that the c.247G>A variant in hMTH1 combined with AluYb8MUTYH variant had a synergistic effect on increasing the risk of T2DM (OR=1.635; 95%CI: 1.147-2.330). This synergy was also observed between the variants in the 5'-UTR of the hOGG1 and the AluYb8MUTYH variant (OR=1.804; 95%CI: 1.254-2.595). Our results suggest, for the first time, the combined effects of AluYb8MUTYH with either hMTH1 c.247G>A or variants in the 5'-UTR of the hOGG1 on the risk of T2DM.
authors: Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
authors: Lili
authors: L
authors: Cao
authors: Wei
authors: W
authors: Zhou
authors: Yanbei
authors: Y
authors: Zhu
authors: Wenwen
authors: W
authors: Guo
authors: Zhenming
authors: Z
authors: Cai
authors: Xuan
authors: X
authors: He
authors: Yuan
authors: Y
authors: Xie
authors: Xinxiu
authors: X
authors: Li
authors: Dalong
authors: D
authors: Zhu
authors: Yaping
authors: Y
authors: Wang
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017382:Reactive Oxygen Species; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D020121:5' Untranslated Regions; D017382:Reactive Oxygen Species; D004247:DNA; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; C479058:oxoguanine glycosylase 1, human; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes