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D2 Dopamine Receptor Alleles Do Not Influence Severity of Tourette's Syndrome: Results From Four Large Kindreds

D2 Dopamine Receptor Alleles Do Not Influence Severity of Tourette's Syndrome: Results From Four... Abstract Objective: We investigated the recently proposed hypothesis that the Al allele of the Taq I polymorphic system at the D2 dopamine receptor gene (DRD2) influences the severity of Tourette's syndrome (TS). We have previously demonstrated that DRD2 is not linked to TS, establishing that it cannot be the major locus determining the susceptibility to develop TS. Method: We studied alleles at the DRD2 A system in patients with TS or chronic multiple tics in four extended kindreds segregating TS. If this allelic system at DRD2 is associated with severity of TS, then among affected family members, those with the Al allele should have more severe disease than those without it. Severity of disease was compared in affected members of the kindreds with Al alleles and in those without Al alleles. Results: We evaluated disease severity in two ways. First, we evaluated 17 individuals from two families using a derivative of the Yale Global Tic Severity Scale composed of subscales concerning number, frequency, and severity of motor and phonic tics, rated separately. We divided this sample (n=17, nine with TS and eight with chronic multiple tics) by genotype at the A1/A2 system. The heterozygotes (n=7) had an average severity score of 11.3; the A2 homozygotes had an average severity score of 14.2. (There were no A1 homozygotes.) Second, we evaluated 47 individuals from two different families (all with TS) using the TS symptomatology evaluation. We compared severity scores for these individuals by genotype at the A1/A2 system. The heterozygotes (n=24) had a mean severity score of 2.8, the A1 homozygotes (n=2) had a mean severity score of 3.0, and the A2 homozygotes (N=21) had a mean severity score of 3.7. Conclusion: Our data do not support alleles at the A system of DRD2 as a factor associated with severity of TS. References 1. Gelernter J, Pakstis AJ, Pauls DL, et al. Gilles de la Tourette syndrome is not linked to D2 dopamine receptor . Arch Gen Psychiatry . 1990;47:1073-1077.Crossref 2. Moises HW, Gelernter J, Giuffra LA, etal. No linkage between D2-dopamine receptor gene region and schizophrenia . Arch Gen Psychiatry . 1991;48:643-647.Crossref 3. Blum K, Noble EP, Sheridan PJ, et al. Allelic association of human dopamine D2 receptor gene in alcoholism . JAMA . 1990:263:2055-2060.Crossref 4. Gelernter J, O'Malley S, Risch N, et al. No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism . JAMA . 1991;266:1801-1807.Crossref 5. Bolos AM, Dean M, Lucas-Derse S, Ramsburg M, Brown GL, Goldman D. Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism . JAMA . 1990;264:3156-3160.Crossref 6. Parsian A, Todd RD, Devor E, et al. Alcoholism and alleles of the human dopamine D2 receptor locus: studies of association and linkage . Arch Gen Psychiatry . 1991;48:655-663.Crossref 7. Blum K, Noble EP, Sheridan PJ, et al. Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism . Alcohol . 1991;8:409-416.Crossref 8. Schwab S, Soyka M, Niederecker M, Ackenheil M, Scherer J, Wildenauer DB. Allelic association of human D2-receptor DNA polymorphism ruled out in 45 alcoholics . Am J Hum Genet . 1991;49( (suppl 4) ):203. Abstract. 9. Turner E, Ewing J, Shilling P, et al. Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism . Biol Psychiatry . 1992; 31:285-290.Crossref 10. Cook BL, Wang ZW, Crowe RR, Hauser R, Freimer M. Alcoholism and the D2 receptor gene . Alcohol Clin Exp Res . 1992;4:806-809.Crossref 11. Goldman D, Dean M, Brown GL, et al. D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in Finland and the United States . Acta Psychiatr Scand . 1992;86:351-357.Crossref 12. Goldman D, Brown GL, Albaugh B, et al. DRD2 dopamine receptor genotype, linkage disequilibrium and alcoholism in American Indians and other populations . Alcoholism . 1993;17:199-204.Crossref 13. Gelernter J, Goldman D, Risch N. The A1 allele at the D2 dopamine receptor gene and alcoholism: a reappraisal . JAMA . 1993;269:1673-1677.Crossref 14. Comings DE, Comings BG, Muhleman D, et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders . JAMA . 1991;266:1793-1800.Crossref 15. Kurlan R, Behr J, Medved L, et al. Familial Tourette's syndrome: report of a large pedigree and potential for linkage analysis . Neurology . 1986;36:772-776.Crossref 16. Pauls DL, Leckman JF. The inheritance of Gilles de la Tourette's syndrome and associated behaviors . N Engl J Med . 1986;315:993-997.Crossref 17. Pauls DL, Raymond CL, Stevenson JM, Leckman JF. A family study of Gilles de la Tourette syndrome . Am J Hum Genet . 1991;48:154-163. 18. Price RA, Kidd KK, Cohen DJ, Pauls DL, Leckman JF. A twin study of Tourette syndrome . Arch Gen Psychiatry . 1985;42:815-820.Crossref 19. Leckman JF, Riddle MA, Hardin MT, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity . J Am Acad Child Adolesc Psychiatry . 1989;28:566-573.Crossref 20. Grandy DK, Litt M, Allen L, et al. The human dopamine D2 receptor gene is located in chromosome 11 at q22-q23 and identifies a Taq I polymorphism . Am J Hum Genet . 1989;45:778-785. 21. Devor EJ. The D2 dopamine receptor and Tourette's syndrome . JAMA . 1992; 267:651.Crossref 22. Comings D. The D2 dopamine receptor and Tourette's syndrome . JAMA . 1992; 267:652.Crossref 23. Cloninger CR. D2 dopamine receptor gene is associated but not linked with alcoholism . JAMA . 1991;266:1833-1834.Crossref 24. Hauge XY, Grandy DK, Eubanks JH, Evans GA, Civelli O, Litt M. Detection and characterization of additional DNA polymorphisms in the dopamine D2 receptor gene . Genomics . 1991;10:527-530.Crossref 25. Sarkar G, Kapelner S, Grandy DK, et al. Direct sequencing of the dopamine D2 receptor (DRD2) in schizophrenics reveals three polymorphisms but no structural change in the receptor . Genomics . 1991;11:8-14.Crossref 26. Kidd KK. Associations of disease with genetic markers: déjá vu all over again . Neuropsychiatr Gen . 1993:48:71-73.Crossref 27. Falk CT, Rubinstein P. Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations . Ann Hum Genet . 1987;51:227-233.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

D2 Dopamine Receptor Alleles Do Not Influence Severity of Tourette's Syndrome: Results From Four Large Kindreds

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/lp/american-medical-association/d2-dopamine-receptor-alleles-do-not-influence-severity-of-tourette-s-T79U0c7BDv
Publisher
American Medical Association
Copyright
Copyright © 1994 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1994.00540160099012
Publisher site
See Article on Publisher Site

Abstract

Abstract Objective: We investigated the recently proposed hypothesis that the Al allele of the Taq I polymorphic system at the D2 dopamine receptor gene (DRD2) influences the severity of Tourette's syndrome (TS). We have previously demonstrated that DRD2 is not linked to TS, establishing that it cannot be the major locus determining the susceptibility to develop TS. Method: We studied alleles at the DRD2 A system in patients with TS or chronic multiple tics in four extended kindreds segregating TS. If this allelic system at DRD2 is associated with severity of TS, then among affected family members, those with the Al allele should have more severe disease than those without it. Severity of disease was compared in affected members of the kindreds with Al alleles and in those without Al alleles. Results: We evaluated disease severity in two ways. First, we evaluated 17 individuals from two families using a derivative of the Yale Global Tic Severity Scale composed of subscales concerning number, frequency, and severity of motor and phonic tics, rated separately. We divided this sample (n=17, nine with TS and eight with chronic multiple tics) by genotype at the A1/A2 system. The heterozygotes (n=7) had an average severity score of 11.3; the A2 homozygotes had an average severity score of 14.2. (There were no A1 homozygotes.) Second, we evaluated 47 individuals from two different families (all with TS) using the TS symptomatology evaluation. We compared severity scores for these individuals by genotype at the A1/A2 system. The heterozygotes (n=24) had a mean severity score of 2.8, the A1 homozygotes (n=2) had a mean severity score of 3.0, and the A2 homozygotes (N=21) had a mean severity score of 3.7. Conclusion: Our data do not support alleles at the A system of DRD2 as a factor associated with severity of TS. References 1. Gelernter J, Pakstis AJ, Pauls DL, et al. Gilles de la Tourette syndrome is not linked to D2 dopamine receptor . Arch Gen Psychiatry . 1990;47:1073-1077.Crossref 2. Moises HW, Gelernter J, Giuffra LA, etal. No linkage between D2-dopamine receptor gene region and schizophrenia . Arch Gen Psychiatry . 1991;48:643-647.Crossref 3. Blum K, Noble EP, Sheridan PJ, et al. Allelic association of human dopamine D2 receptor gene in alcoholism . JAMA . 1990:263:2055-2060.Crossref 4. Gelernter J, O'Malley S, Risch N, et al. No association between an allele at the D2 dopamine receptor gene (DRD2) and alcoholism . JAMA . 1991;266:1801-1807.Crossref 5. Bolos AM, Dean M, Lucas-Derse S, Ramsburg M, Brown GL, Goldman D. Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism . JAMA . 1990;264:3156-3160.Crossref 6. Parsian A, Todd RD, Devor E, et al. Alcoholism and alleles of the human dopamine D2 receptor locus: studies of association and linkage . Arch Gen Psychiatry . 1991;48:655-663.Crossref 7. Blum K, Noble EP, Sheridan PJ, et al. Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism . Alcohol . 1991;8:409-416.Crossref 8. Schwab S, Soyka M, Niederecker M, Ackenheil M, Scherer J, Wildenauer DB. Allelic association of human D2-receptor DNA polymorphism ruled out in 45 alcoholics . Am J Hum Genet . 1991;49( (suppl 4) ):203. Abstract. 9. Turner E, Ewing J, Shilling P, et al. Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism . Biol Psychiatry . 1992; 31:285-290.Crossref 10. Cook BL, Wang ZW, Crowe RR, Hauser R, Freimer M. Alcoholism and the D2 receptor gene . Alcohol Clin Exp Res . 1992;4:806-809.Crossref 11. Goldman D, Dean M, Brown GL, et al. D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in Finland and the United States . Acta Psychiatr Scand . 1992;86:351-357.Crossref 12. Goldman D, Brown GL, Albaugh B, et al. DRD2 dopamine receptor genotype, linkage disequilibrium and alcoholism in American Indians and other populations . Alcoholism . 1993;17:199-204.Crossref 13. Gelernter J, Goldman D, Risch N. The A1 allele at the D2 dopamine receptor gene and alcoholism: a reappraisal . JAMA . 1993;269:1673-1677.Crossref 14. Comings DE, Comings BG, Muhleman D, et al. The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders . JAMA . 1991;266:1793-1800.Crossref 15. Kurlan R, Behr J, Medved L, et al. Familial Tourette's syndrome: report of a large pedigree and potential for linkage analysis . Neurology . 1986;36:772-776.Crossref 16. Pauls DL, Leckman JF. The inheritance of Gilles de la Tourette's syndrome and associated behaviors . N Engl J Med . 1986;315:993-997.Crossref 17. Pauls DL, Raymond CL, Stevenson JM, Leckman JF. A family study of Gilles de la Tourette syndrome . Am J Hum Genet . 1991;48:154-163. 18. Price RA, Kidd KK, Cohen DJ, Pauls DL, Leckman JF. A twin study of Tourette syndrome . Arch Gen Psychiatry . 1985;42:815-820.Crossref 19. Leckman JF, Riddle MA, Hardin MT, et al. The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity . J Am Acad Child Adolesc Psychiatry . 1989;28:566-573.Crossref 20. Grandy DK, Litt M, Allen L, et al. The human dopamine D2 receptor gene is located in chromosome 11 at q22-q23 and identifies a Taq I polymorphism . Am J Hum Genet . 1989;45:778-785. 21. Devor EJ. The D2 dopamine receptor and Tourette's syndrome . JAMA . 1992; 267:651.Crossref 22. Comings D. The D2 dopamine receptor and Tourette's syndrome . JAMA . 1992; 267:652.Crossref 23. Cloninger CR. D2 dopamine receptor gene is associated but not linked with alcoholism . JAMA . 1991;266:1833-1834.Crossref 24. Hauge XY, Grandy DK, Eubanks JH, Evans GA, Civelli O, Litt M. Detection and characterization of additional DNA polymorphisms in the dopamine D2 receptor gene . Genomics . 1991;10:527-530.Crossref 25. Sarkar G, Kapelner S, Grandy DK, et al. Direct sequencing of the dopamine D2 receptor (DRD2) in schizophrenics reveals three polymorphisms but no structural change in the receptor . Genomics . 1991;11:8-14.Crossref 26. Kidd KK. Associations of disease with genetic markers: déjá vu all over again . Neuropsychiatr Gen . 1993:48:71-73.Crossref 27. Falk CT, Rubinstein P. Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations . Ann Hum Genet . 1987;51:227-233.Crossref

Journal

Archives of NeurologyAmerican Medical Association

Published: Apr 1, 1994

References

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