AluYb8 insertion in the MUTYH gene is related to increased 8-OHdG in genomic DNA and could be a risk factor for type 2 diabetes in a Chinese population.
The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Because oxidative stress may contribute to increased diabetes risk, the common variant of the MUTYH gene (AluYb8MUTYH) was investigated for its possible role in type 2 diabetes mellitus (T2DM). A total of 565 T2DM patients and 565 healthy subjects from China were enrolled in a case-control study. The distribution of AluYb8MUTYH differed in diabetic patients from controls, with a moderately increased percentage of the mutant allele (P) (44.7% versus 40.3%, P = 0.033, OR = 1.199). However, this distribution was similar between the diabetic early-onset and late-onset subgroups. Another 66 T2DM patients were further evaluated for 8-hydroxy-2'deoxyguanosine (8-OHdG) levels in leukocytic DNA. The average value of 8-OHdG/10(6) dG was 10.4 in patients with the wild-type genotype, 15.9 in heterozygotes, and 22.3 in homozygotes with the variation (P < 0.001, compared with the wild-type). Therefore, the AluYb8MUTYH polymorphism could be a novel genetic risk factor for T2DM, and accumulated 8-OHdG could contribute to this disease.
Department of Medical Genetics, Nanjing University School of Medicine, Nanjing, China; Jiangsu Key Lab of Molecular Medicine, Nanjing University, Nanjing, China.
Huimei
H
Chen
Caixia
C
Sun
Wenwen
W
Guo
Ran
R
Meng
Hong
H
Du
Qiufeng
Q
Qi
Xin
X
Gu
Lirong
L
Li
Kui
K
Zhang
Dalong
D
Zhu
Yaping
Y
Wang
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D004247:DNA / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D011110:Polymorphism, Genetic; D012307:Risk Factors
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D045647:DNA Glycosylases; C061738:mutY adenine glycosylase; D003849:Deoxyguanosine