Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
권호 표지

Linkage Disequilibrium of Dopamine D2 Receptor Gene in the Korean Population

  • Published : 2004.03.01
Download PDF
⟨ Previous Next ⟩

Abstract

The genetic basis of hypertension is complex, and has been considered to be associated with the dopamine D2 receptor gene (DD2R). Because association studies using the candidate gene approach may provide important clues regarding the pathogenesis of hypertension and establish basis for further study, we performed the association study on the relationship between genetic polymorphisms in the DD2R gene and hypertension in Koreans. Eighty nine patients with hypertension and 86 age-matched subjects with normal blood pressure were enrolled. Genomic DNA was extracted from peripheral blood leukocytes. PCR-RFLP analysis was performed to detect the three polymorphic Taq I sites in the DD2R gene. There were no significant differences in genotype, allele and haplotype distributions of any polymorphisms in the DD2R gene between two groups, respectively (P>0.05), although significant linkage disequilibriums among these polymorphic sites were detected by pair-wise analysis (P<0.05). Therefore, our negative result suggest that the three Taq I RFLPs in the DD2R gene were not significantly associated with hypertension in Koreans.

Keywords

References

  1. Bostein, D., White, R.L., Skolnick, M. and Davis, R.W. (1980): Construction of a genetic linkage map using restriction fragment length polymorphisms, Am. J. Hum. Genet., 32, 314-331
  2. Blum, K., Noble, E.P., Sheridan, P.J., Montgomery, A., Ritchie, T., Ozkaragoz, T., Fitch, R.J., Wood, R., Finley, O. and Sadlack, F. (1993): Genetic predisposition in alcholism: association of the D2 dopamine receptor Taq IB RFLP with severe alcoholics, Alcohol, 10, 59-67
  3. Comings, D.E., Flanagan, S.D., Dietz, G., Muhleman, D., Knell, E. and Gysin, R. (1993): The dopamine D2 recep-tor (DRD2) as a major gene in obesity and height, Bio-chem. Med. Metab. Biol., 50, 176-185
  4. Cravchik, A., Sibley, D.R. and Gejman, P.V. (1996): Func-tional analysis of the human D2 dopamine receptor mis-sense variants, J. Biol. Chem., 271, 26013-26017 https://doi.org/10.1074/jbc.271.42.26013
  5. Di Lella, A.G., Marvit, J., Lidsky, A.S., Guttler, F. and Woo, S.L.C. (1986): Tight linkage between a splicing mutation and a specific DNA haplotype in phenylketonuria, Nature, 322, 799-803
  6. Friedewald, W.T., Levy, R.L. and Friedrickson, D.S. (1972): Estimation of the concentration of low-density lipoprotein cholesterol in plasma without the use of the preparative ultracentrifuge, Clin. Chem., 18, 499-502
  7. Grandy, D.K., Litt, M., Allen, L., Bunzow, J.R., Marchionni, M., Makam, H., Reed, L., Magenis, R.E. and Civelli, O. (1989a): The human dopamine receptor gene is located on chromosome 11 at q22-q23 and identifies a Taq I RFLP, Am. J. Hum. Genet., 45, 778-785
  8. Grandy, D.K., Marchionni, M., Makam, H., Stofko, R.E., Alfano, M., Frothingham, L., Fischer, J.B., Burke-Howie, K.J., Bunzow, J.R., Server, AC., Magenis, R.E. and Civ-elli, O. (1989b): Cloning of the cDNA and gene for a human D2 dopamine receptor, Proc. Natl. Acad. Sci. USA, 86, 9762-9766
  9. Hill, W.G. and Robertson, A. (1968): Linkage disequilibrium of finite populations, Theor. Appl. Genet., 38, 226-231
  10. Hussain, T. and Lokhandwala, M.F. (1998): Renal dopamine receptor function in hypertension, Hypertension, 32, 187-197
  11. Jose, P.A., Drago, J., Accili, D., Eisner, G.M. and Felder, R.A. (1997): Transgenic mice to study the role of dopamine receptors in cardiovascular function, Clin. Exp. Hypertens. [A], 19, 15-25.
  12. Kren, V., Pravenec, M., Lu, S.H., Krenova, D., Wang, J.M., Wang, N., Merriouns, T., Wong, A., St. Lezin, E., Lau, D., Szpirer, C., Szpirer, J. and Krutz, T.W. (1997): Genetic isolation of a region of chromosome 8 that exerts major effects on blood pressure and cardiac mass in the spon-taneously hypertensive rat, J. Clin. Invest., 99, 577-581 https://doi.org/10.1172/JCI119198
  13. Lewontin, R.C. (1964): The interaction of selection and link-age. I. General considerations: heterotic models, Genetics, 49, 49-67
  14. Mannelli, M., Lazzeri, C., lanni, L., La Villa, G., Pupilli, C., Bellini, F., Serio, M. and Franchi, F. (1997): Dopamine and sympathoadrenal activity in man, Clin. Exp. Hypertens. [A], 19, 163-179.
  15. Mosterd, A., DAgostino, R.B., Sibershatz, H., Sytkowski, P.A. and Kannel, W.B. (1999): Trends in the prevalence of hypertension, antihypertensive therapy, and left ventricu-lar hypertrophy from 1950 to 1989, N. Engl. J. Med., 340, 1221-1227 https://doi.org/10.1056/NEJM199904223401601
  16. Nam, Y.S. and Lee, C. (1997): Genetic variations at the dopamine D2 receptor locus in Korean population, Korean J. Genetics, 19, 289-297
  17. OHara, B.F., Smith, S.S., Bird, G., Persico, A.M., Suarez, B.K., Cutting, G.R. and Uhl, G.R. (1993): Dopamine D2 receptor RFLPs, haplotypes and their association with substance use in Black and Caucasian research volun-teers, Hum. Hered., 43, 209-218
  18. Rosmond, R., Rankinen, T., Chagnon, M., Perusse, L., Chag-non, Y.C., Bouchard, C. and Biomtorp, P. (2001): Poly-morphism in exon 6 of the dopamine D(2) receptor gene (DRD2) is associated with elevated blood pressure and personality disorders in men, J. Hum. Hypertens., 15, 553-558 https://doi.org/10.1038/sj.jhh.1001231
  19. Sibley, D.R. and Monsma, F.J. Jr. (1992) Molecular biology of dopamine receptors, Trends Pharmacol. Sci., 13, 61-69
  20. Thomas, G.N., Tomlinson, B. and Critchley, A.J.H. (2000): Modulation of blood pressure and obesity with the dopamine D2 receptor gene Taq I polymorphism, Hypertension, 36, 177-182