Association of the PIK3C2G gene polymorphisms with type 2 DM in a Japanese population

被引:26
作者
Daimon, Makoto [1 ,2 ]
Sato, Hidenori [3 ]
Oizumi, Toshihide [1 ]
Toriyama, Sayumi [3 ]
Saito, Takafumi [2 ]
Karasawa, Shigeru [1 ]
Jimbu, Yumi [1 ]
Wada, Kiriko [1 ]
Kameda, Wataru [1 ]
Susa, Shinji [1 ]
Yamaguchi, Hiroshi [1 ]
Emi, Mitsuru [3 ]
Muramatsu, Masaaki [3 ,4 ]
Kubota, Isao [2 ]
Kawata, Sumio [2 ]
Kato, Takeo [1 ,2 ]
机构
[1] Yamagata Univ, Sch Med, Dept Neurol Hematol Metabol Endocrinol & Diabetol, Yamagata 9909585, Japan
[2] Yamagata Univ, Sch Med, 21st Century Ctr Excellence Program Study Grp, Yamagata, Japan
[3] HuBit Genom Res Inst, Tokyo, Japan
[4] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Epidemiol, Tokyo, Japan
关键词
PI3; kinase; PIK3C2G; quantitative association study; serum insulin levels; community-based study; haplotype and diplotype analysis;
D O I
10.1016/j.bbrc.2007.10.180
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
The associations of five SNPs (SNPsl-5: A-5468G, A-3333G, C-1794T, C437T and T9148C) of the class 11 phosphoinositide 3-kinase gamma-subunit (PIK3C2G) gene with type 2 diabetes were examined using a population of the Takahata Study (n (M/W): 2930 (1328/1602); age: 63.3 +/- 10.2 years), a Japanese community-based study. Quantitative association study of the SNPs with HbAlc levels showed significant association for SNPs 2 and 4 (p = 0.018 and 0.004, respectively). A case-control association study of SNP 4 with diabetes by multiple logistic regression analysis showed a significant association of the genotype TT of the SNP with an odds ratio of 2.21 (p = 0.001) independently of age, gender and BMI. In the NGT subjects, serum fasting insulin levels in the at-risk genotype group of SNP 4 were significantly lower than those in the others (TT, TC, and CC, 4.9 +/- 2.6, 5.4 +/- 3.0, and 5.6 +/- 3.4 mu U/ml, respectively; p = 0.029). (c) 2007 Elsevier Inc. All rights reserved.
引用
收藏
页码:466 / 471
页数:6
相关论文
共 24 条
[1]
Alberti KGMM, 1998, DIABETIC MED, V15, P539, DOI 10.1002/(SICI)1096-9136(199807)15:7<539::AID-DIA668>3.0.CO
[2]
2-S
[3]
Candidate gene association study in type 2 diabetes indicates a role for genes involved in β-cell function as well as insulin action [J].
Barroso, I ;
Luan, J ;
Middelberg, RPS ;
Harding, AH ;
Franks, PW ;
Jakes, RW ;
Clayton, D ;
Schafer, AJ ;
O'Rahilly, S ;
Wareham, NJ .
PLOS BIOLOGY, 2003, 1 (01) :41-55
[4]
Insulin activates the α isoform of class II phosphoinositide 3-kinase [J].
Brown, RA ;
Domino, J ;
Arcaro, A ;
Waterfield, MD ;
Shepherd, PR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (21) :14529-14532
[5]
Growth factor regulation of the novel class II phosphoinositide 3-kinases [J].
Brown, RA ;
Shepherd, PR .
BIOCHEMICAL SOCIETY TRANSACTIONS, 2001, 29 :535-537
[6]
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism [J].
Engelman, Jeffrey A. ;
Luo, Ji ;
Cantley, Lewis C. .
NATURE REVIEWS GENETICS, 2006, 7 (08) :606-619
[7]
The phosphoinositide (PI) 3-kinase family [J].
Foster, FM ;
Traer, CJ ;
Abraham, SM ;
Fry, MJ .
JOURNAL OF CELL SCIENCE, 2003, 116 (15) :3037-3040
[8]
Identification of a common amino acid polymorphism in the p85 alpha regulatory subunit of phosphatidylinositol 3-kinase - Effects on glucose disappearance constant, glucose effectiveness, and the insulin sensitivity index [J].
Hansen, T ;
Andersen, CB ;
Echwald, SM ;
Urhammer, SA ;
Clausen, JO ;
Vestergaard, H ;
Owens, D ;
Hansen, L ;
Pedersen, O .
DIABETES, 1997, 46 (03) :494-501
[9]
HOD LK, 1997, BIOCHEM BIOPH RES CO, V235, P130
[10]
Cellular function of phosphoinositide 3-kinases: Implications for development, immunity, homeostasis, and cancer [J].
Katso, R ;
Okkenhaug, K ;
Ahmadi, K ;
White, S ;
Timms, J ;
Waterfield, MD .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2001, 17 :615-675