Environmental Analysis Health and Toxicology

환경독성보건학회 (The Korean Society of Environmental Health and Toxicology)
권호 표지

한국인에서 Paraoxonase-2 유전자의 Codon 311 다형성에 관한 연구

Codon 311 Polymorphism of Paraoxonase-2 Gene and Hypertension in Korean

  • 장대호 (삼육대학교 생명과학과) ;
  • 강병용 (삼육대학교 생명과학연구소) ;
  • 이강오 (삼육대학교 생명과학과)
  • 발행 : 2004.06.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

고혈압에서 지질대사 이상은 빈번히 나타나는 현상으로, 지질대사 이상에 관여하는 유전자들은 고혈압의 발병원인을 규명하기 위한 후보 유전자로 인식되어 왔다. 이에 본 연구에서는 paraoxonase 2(PON2) 유전자에 존재하는 Cys311Ser다형성을 유전자 표지로 이용하여 한국인 집단에서 이 유전자 표지가 고혈압과 관련성이 있는 지를 조사하고자 하였다. 연구 대상은 총 195명으로, 이들 중에서 82명은 고혈압 환자 군이었고, 나머지 113명은 정상 혈압 군이었다. PON2 유전자의 Cys311Ser 다형성을 분석하기 위해서 중합효소 연쇄반응과 제한 효소인 Dde Ⅰ처리를 수행하여 유전자형을 결정하였다. 연구 결과, Cys/Ser이 형접합체를 갖는 사람들이 고혈압군에서 유의하게 높은 빈도로 나타났으며(P<0.05),다른 신체 계측치 및 혈청내 지질 농도와는 유의한 관련성을 나타내지 않았다. 본 연구에서 관찰된 이러한 관련성이 기능적인 연관인지 혹은 연관불평형에 의한 결과인지에 대해서는 보다 더 많은 연구 대상을 이용한 추시를 통해 밝혀질 수 있을 것으로 생각된다.

키워드

참고문헌

  1. Blatter M-C, James RW, Messmer S, Barja F and Pornetta D. Identification of a distinct high-density lipoprotein subspecies defined by a lipoproteinassociated protein, K-45. Identity of K-45 with paraoxonase, Eur. J. Biochem. 1993; 211: 871-879 https://doi.org/10.1111/j.1432-1033.1993.tb17620.x
  2. Bostein D, White RL, Skolnick M and Davis RW. Construction of a genetic linkage map in man using restriction fragment length polymorphisms, Am. J. Hum. Genet. 1980; 3: 314-331
  3. Bray MS, Krushkal J, Li L, Ferrell R, Kardia S, Sing CF, Tumer ST and Boerwinkle E.: Positional genomic analy-sis identifies the $\beta$2-adrenergic receptor gene as a suscep-tibility locus for hypertension, Circulation 2000; 101: 2877-2882 https://doi.org/10.1161/01.CIR.101.25.2877
  4. Campo S, Sardo AM, Campo GM, Avenoso A, Castaldo M, D'Ascola A, Giunta E, Calatroni A and Saitta A. Identifi-cation of paraoxonase 3 gene (PON3) missense muta-tions in a population of southern Italy, Mutation Res 2004; 546: 75-80 https://doi.org/10.1016/j.mrfmmm.2003.11.007
  5. Choi TY, Lee YK, Kim WB, Lee DW, Hyon MS, Seo SW, Kim SK and Kwon YJ. A study on gene frequency of paraoxonase gene 2 in patients with coronary heart disease, Korean J. Clin. Pathol. 1999; 19: 420-424
  6. Cusi D, Barlassina C, Azzani T, Casari G, Citterio L, Devoto M, Gloriso N, Lanzani C, Manunta P, Righetti M, Rivera R, Stella P, Troffa C, Zagato L and Bianchi G. Polymorphisms of $\alpha$-adducin and salt sensitivity in patients with essential hypertension, Lancet 1997; 349: 1353-1357 https://doi.org/10.1016/S0140-6736(97)01029-5
  7. Fridewald WT, Levy RI and Friedrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of the preparative ultracen trifuge, Clin. Chem. 1972; 18: 499-502
  8. Furlong CE, Richter RJ, Seidel SJ and Motulsky A. Role of genetic polymorphism of human plasma paraoxonase/ arylesterase in hydrolysis of the insecticide metabolites chlorpyrifos oxon and paraoxon, Am. J. Hum. Genet. 1988; 43: 230-238
  9. Hong SH, Song J, Min WK and Kim JQ. Genetic variations of the paraoxonase gene in patients with coronary artery disease, Clin. Biochem. 2001; 34: 475-481 https://doi.org/10.1016/S0009-9120(01)00257-0
  10. Izawa H, Yamada Y, Okada T, Tanaka M, Hirayama H and Yokota M. Prediction of genetic risk for hypertension, Hypertension 2003; 41: 1035-1040 https://doi.org/10.1161/01.HYP.0000065618.56368.24
  11. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams, CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel J-M and Corvol P. Molecular basis of human hypertension: role of angiotensinogen, Cell 1992; 71: 169-180 https://doi.org/10.1016/0092-8674(92)90275-H
  12. Kang BY, Kim KT, Shin JH, Om AS and Lee CC. The association between codon 192 polymorphism of paraox-onase/arylesterase gene and plasma HDL-cholesterol level in Korean population, Environ. Mutagens Carcinogens 2001; 21: 9-13
  13. La Du BN, Aviram M, Billecke S, Navab M, Primo-Parma S, Sorenson RC and Standiford TJ. On the physiological role(s) of the paraoxonase, Chemico-Biol. Interac. 1999; 119-120, 379-388 https://doi.org/10.1016/S0009-2797(99)00049-6
  14. Leus FR, Zwart M, Kastelein JJ P and Voorbij HAM. $PON_2$ gene variants are associated with clinical manifestations of cardiovascular disease in familial hypercholesterolemia patients, Atherosclerosis 2001; 154: 641-649 https://doi.org/10.1016/S0021-9150(00)00440-8
  15. Lifton RP, Gharavi AG and Geller DS. Molecular mecha-nisms of human hypertension, Cell 2001; 104: 545-556 https://doi.org/10.1016/S0092-8674(01)00241-0
  16. Mackness MI, Arrol S, Abbott CA and Dumngton PN. Is paraoxonase related to atherosclerosis? Chemico-Biol. Interac. 1993; 87: 161-171 https://doi.org/10.1016/0009-2797(93)90038-Z
  17. Mackness MI, Mackness B and Durrington PN. Paraoxonase and coronary heart disease, Atherosclerosis 2002; Suppl 3: 49-55 https://doi.org/10.1016/S1567-5688(02)00046-6
  18. Malin R, Rantalaiho V, Huang X-H, Wirta O, Pasternack A, Leinonen JS, Alho H, Jokela H, Koivula T, Tanaka T, Okada K, Ochi H, Toyokuni S and Lehtimaki T. Associ-ation between M/L55-polymorphism of paraoxonase enzyme and oxidative DNA damage in patients with type 2 diabetes mellitus and in control subjects, Hum. Genet. 1999: 105: 179-180
  19. Motti C, Dessi M, Gnasso A, Irace C, Indigene P, Angelucci CB, Bemardini S, Fucci G, Federici G and Cortese CA multiplex PCR-based DNA assay for the detection of paraoxonase gene cluster polymorphisms, Atherosclerosis 2001; 158: 35-40 https://doi.org/10.1016/S0021-9150(00)00765-6
  20. Primo-Parma SL, Sorenson RC, Teiber J and La Du BN. The human serum paraoxonase/arylesterase gene (PON1) is one member of a multigene family, Genomics 1996; 33: 498-509 https://doi.org/10.1006/geno.1996.0225
  21. Sambrook J, Fritsch EF and Maniatis T. Molecular Cloning -A Laboratory Manual. 2nd ed. Cold Spring Harbor NY, pp. 9.16-9.23
  22. Sanghera DK, Aston CE, Saha N and K.amboh MI. DNA polymorphisms in two paraoxonase genes (PON1 and PON2) are associated with the risk of coronary heart disease, Am. J. Hum. Genet. 1988; 62: 36-44 https://doi.org/10.1086/301669
  23. Serrato M and Marian AJ. A variant of human paraoxonase/arylesterase (HUMPONA) gene is a risk factor for coro-nary arteru disease, J. Clin. Invest. 1995; 96: 3005-3008 https://doi.org/10.1172/JCI118373
  24. Shi J, Zhang S, Tang M, Liu X, Li X, Li T, Han H, Wang Y, Guo Y, Zhao J, Li Hai and Ma C. Possible association between Cys311Ser polymorphism of paraoxonase 2 gene and late-onset Alzheimer's disease in Chinese, Mol. Brain Res. 2004; 120: 201-204 https://doi.org/10.1016/j.molbrainres.2003.10.018
  25. Siffert W, Rosskop D, Siffert G, Busch S, Moritz A, Erbel R, Sharma AM, Ritz E, Wichmann H-E, Jakobs KH and Horsthemke B. Association of a human G-protein $beta$3 subunit variant with hypertension, Nat. Genet. 1998; 18: 45-48 https://doi.org/10.1038/ng0198-45