Matrix Metallopeptidase 2 Gene Polymorphism is Associated with Obesity in Korean Population

  • Han, Dong-Hee (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kim, Su-Kang (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kang, Sung-Wook (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Choe, Bong-Keun (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University) ;
  • Kim, Keon-Sik (Departments of Anesthesiology and Pain Medicine, School of Medicine, Kyung Hee University) ;
  • Chung, Joo-Ho (Kohwang Medical Research Institute, School of Medicine, Kyung Hee University)
  • Published : 2008.06.30

Abstract

The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of matrix metallopeptidase 2 (MMP2) are associated with obesity. MMP2 is an enzyme with proteolytic activity against matrix and nonmatrix proteins, particularly basement membrane constituents. To identify the relationship between polymorphisms of MMP2 and overweight/obese, we genotyped 5 SNPs (rs17242319, rs1053605, rs243849, rs2287074, and rs10775332) of the coding region of MMP2 using the Golden Gate assay on an Illumina BeadStation 500 GX. One hundred and forty two overweight/obese ($BMI\;{\ge}\;23$) and 145 normal (BMI 18 to < 23) subjects were analyzed. SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs were used for the analysis of genetic data. A linkage disequilibrium (LD) block was discovered among the 5 SNPs selected, including rs17242319, rs1053605, rs243849, and rs2287074. Of the 5 polymorphisms, 2 synonymous SNPs [rs17242319 (Gly226Gly) and rs10775332 (Phe602Phe)] were found significant associations with overweight/obese. Recently, rs1132896 replaced rs17242319 as a new number (SNP database, BUILD 129). In haplotype analysis using Haploview, a haplotype (haplotype: CCCA) containing a meaningful polymorphism (rs17242319) was found to be significantly different. The results suggest that MMP2 may be associated with overweight/obese in Korean population.

Keywords

References

  1. Aranceta J, Perez-Rodrigo C, Serra-Majem L, Bellido D, de la Torre ML, Formiguera X, Moreno B. Prevention of overweight and obesity: a Spanish approach. Public Health Nutrition 10: 1187− 1193, 2007
  2. Bajaj M, Suraamornkul S, Pratipanawatr T, Hardies LJ, Pratipanawatr W, Glass L, Cersosimo E, Miyazaki Y, DeFronzo RA. Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes 52: 1364−1370, 2003
  3. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics (Oxford, England) 21: 263−265, 2005
  4. Barsh GS, Farooqi IS, O'Rahilly S. Genetics of body-weight regulation. Nature 404: 644−651, 2000
  5. Clement K, Langin D. Regulation of inflammation-related genes in human adipose tissue. Journal of Internal Medicine 262: 422−430, 2007
  6. Cota D, Proulx K, Seeley RJ. The role of CNS fuel sensing in energy and glucose regulation. Gastroenterology 132: 2158−2168, 2007
  7. Dong C, Li WD, Geller F, Lei L, Li D, Gorlova OY, Hebebrand J, Amos CI, Nicholls RD, Price RA. Possible genomic imprinting of three human obesity-related genetic loci. American Journal of Human Genetics 76: 427−437, 2005
  8. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behavior Research Methods 39: 175−191, 2007
  9. Gremlich S, Nguyen D, Reymondin D, Hohlfeld P, Vial Y, Witkin SS, Gerber S. Fetal MMP2/MMP9 polymorphisms and intrauterine growth restriction risk. Journal of Reproductive Immunology 74: 143−151, 2007
  10. Hangauer DG, Monzingo AF, Matthews BW. An interactive computer graphics study of thermolysin-catalyzed peptide cleavage and inhibition by N-carboxymethyl dipeptides. Biochemistry 23: 5730−5741, 1984
  11. Hinterseher I, Bergert H, Kuhlisch E, Bloomenthal A, Pilarsky C, Ockert D, Schellong S, Saeger HD, Krex D. Matrix metalloproteinase 2 polymorphisms in a caucasian population with abdominal aortic aneurysm. The Journal of Surgical Research 133: 121−128, 2006
  12. Lambert JC, Jaffray JY, Michalski JC, Ortonne JP, Paquis V, Saunieres AM. Biochemical and ultrastructural study of two familial cases of Winchester syndrome. Journal de Genetique Humaine 37: 231−236, 1989
  13. Martignetti JA, Aqeel AA, Sewairi WA, Boumah CE, Kambouris M, Mayouf SA, Sheth KV, Eid WA, Dowling O, Harris J, Glucksman MJ, Bahabri S, Meyer BF, Desnick RJ. Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Nature Genetics 28: 261−265, 2001
  14. Martinez-Hernandez A, Enriquez L, Moreno-Moreno MJ, Marti A. Genetics of obesity. Public Health Nutrition 10: 1138−1144, 2007
  15. Mehta S, Farmer JA. Obesity and inflammation: a new look at an old problem. Current Atherosclerosis Reports 9: 134−138, 2007
  16. Miao X, Yu C, Tan W, Xiong P, Liang G, Lu W, Lin D. A functional polymorphism in the matrix metalloproteinase-2 gene promoter (-1306C/T) is associated with risk of development but not metastasis of gastric cardia adenocarcinoma. Cancer Research 63: 3987−3990, 2003
  17. Migrenne S, Magnan C, Cruciani-Guglielmacci C. Fatty acid sensing and nervous control of energy homeostasis. Diabetes & Metabolism 33: 177−182, 2007
  18. Morgunova E, Tuuttila A, Bergmann U, Isupov M, Lindqvist Y, Schneider G, Tryggvason K. Structure of human pro-matrix metalloproteinase-2: activation mechanism revealed. Science (New York, NY) 284: 1667−1670, 1999
  19. Nagase H, Barrett AJ, Woessner JF, Jr. Nomenclature and glossary of the matrix metalloproteinases. Matrix (Stuttgart, Germany) 1: 421−424, 1992
  20. Rouzier C, Vanatka R, Bannwarth S, Philip N, Coussement A, Paquis-Flucklinger V, Lambert JC. A novel homozygous MMP2 mutation in a family with Winchester syndrome. Clinical Genetics 69: 271−276, 2006
  21. Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics (Oxford, England) 22: 1928−1929, 2006
  22. Stephens M, Smith NJ, Donnelly P. A new statistical method for haplotype reconstruction from population data. American Journal of Human Genetics 68: 978−989, 2001
  23. Wilson SG, Adam G, Langdown M, Reneland R, Braun A, Andrew T, Surdulescu GL, Norberg M, Dudbridge F, Reed PW, Sambrook PN, Kleyn PW, Spector TD. Linkage and potential association of obesity-related phenotypes with two genes on chromosome 12q24 in a female dizygous twin cohort. Eur J Hum Genet 14: 340−348, 2006
  24. Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. The Journal of Endocrinology 184: 291−318, 2005
  25. Yu C, Pan K, Xing D, Liang G, Tan W, Zhang L, Lin D. Correlation between a single nucleotide polymorphism in the matrix metalloproteinase-2 promoter and risk of lung cancer. Cancer Research 62: 6430−6433, 2002
  26. Zankl A, Bonafe L, Calcaterra V, Di Rocco M, Superti-Furga A. Winchester syndrome caused by a homozygous mutation affecting the active site of matrix metalloproteinase 2. Clinical Genetics 67: 261−266, 2005
  27. Zhou G, Zhai Y, Cui Y, Qiu W, Yang H, Zhang X, Dong X, He Y, Yao K, Zhang H, Peng Y, Yuan X, Zhi L, Zhang X, He F. Functional polymorphisms and haplotypes in the promoter of the MMP2 gene are associated with risk of nasopharyngeal carcinoma. Human Mutation 28: 1091−1097, 2007