title: Dopamine D3 receptor Ser9Gly and catechol-o-methyltransferase Val158Met polymorphisms and acute pain in sickle cell disease.
abstract: BACKGROUND
  Pain in sickle cell disease (SCD) is characterized by episodes of acute pain, primarily responsible for acute health care utilization, and persistent chronic pain. Pain severity and frequency vary significantly among patients with SCD. In this study, we investigated the possible contribution of monoamine gene polymorphisms to pain variation.
  
  
  METHODS
  Adult subjects with SCD completed PAINReportIt, a computerized McGill Pain Questionnaire, from which we calculated the Composite Pain Index. Utilization data were obtained from the medical record and biweekly telephone calls for 12 months. Utilization is defined as admissions to the emergency department and/or the acute care center resulting from a sickle cell pain crisis. We performed genotyping for catechol-O-methyltransferase (COMT) Val158Met (rs4680) and dopamine D3 receptor (DRD3) Ser9Gly (rs6280) polymorphisms, which were analyzed for associations with pain phenotypes.
  
  
  RESULTS
  Binary logistic models revealed that DRD3 Ser9Gly heterozygote patients were more likely not to have an acute pain crisis (odds ratio [OR] [95% confidence interval {CI}], 4.37 [1.39-22.89]; P = 0.020), which remained so when demographic variables were considered (OR [95% CI], 4.53 [1.41-28.58]; P = 0.016). COMT Val158Met Met allele showed lower probability for zero utilization (OR [95% CI], 0.32 [0.12-0.83]; P = 0.020) than the Val allele. In the negative binomial regression analysis, subjects with COMT Met/Met genotype had utilization incident rate ratio (95% CI) of 2.20 (1.21-3.99) over those with Val/Val (P = 0.010).
  
  
  CONCLUSIONS
  These exploratory findings suggest that DRD3 Ser9Gly and COMT Val158Met may contribute to pain heterogeneity in SCD, as suggested by the different rates of acute pain crisis. Specifically, SCD patients with the DRD3 homozygote genotypes, COMT 158 Met allele or Met/Met genotype, are more likely to have acute care utilization, an indicator of acute pain. These results, however, will need to be further examined in future large prospective studies.
authors.affiliation: From the *Department of Biopharmaceutical Sciences, University of Illinois at Chicago College of Pharmacy; †Department of Biobehavioral Health Science, University of Illinois at Chicago College of Nursing; ‡Division of Hematology/Oncology, University of Illinois at Chicago College of Medicine; §Jesse Brown Veteran's Administration Medical Center; and ∥Cancer Center, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Ellie
authors.initials: E
authors.lastname: Jhun
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Yingwei
authors.initials: Y
authors.lastname: Yao
authors.forename: Robert E
authors.initials: RE
authors.lastname: Molokie
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Wilkie
authors.forename: Zaijie Jim
authors.initials: ZJ
authors.lastname: Wang
mesh_terms: D059787:Acute Pain / Q000209:etiology / Q000235:genetics*; D000328:Adult; D000483:Alleles; D000755:Anemia, Sickle Cell / Q000150:complications / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D010147:Pain Measurement; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D050637:Receptors, Dopamine D3 / Q000235:genetics*
chemical_list: D050637:Receptors, Dopamine D3; D004247:DNA; D002394:Catechol O-Methyltransferase
references.citation: Mol Psychiatry. 1998 Jul;3(4):337-41
references.pmid: 9702743
references.citation: J Natl Med Assoc. 2010 Jan;102(1):18-27
references.pmid: 20158132
references.citation: Pain. 2006 Feb;120(3):230-234
references.pmid: 16427195
references.citation: Med Hypotheses. 2011 Oct;77(4):491-3
references.pmid: 21763079
references.citation: Biochem Biophys Res Commun. 1996 Aug 23;225(3):1068-72
references.pmid: 8780735
references.citation: Mol Psychiatry. 1999 Sep;4(5):484-7
references.pmid: 10523822
references.citation: JAMA. 2010 Apr 7;303(13):1288-94
references.pmid: 20371788
references.citation: J Biol Chem. 1958 Sep;233(3):702-5
references.pmid: 13575440
references.citation: J Pain Symptom Manage. 2003 Mar;25(3):213-24
references.pmid: 12614956
references.citation: Psychiatr Genet. 2004 Mar;14(1):9-12
references.pmid: 15091310
references.citation: Pain. 1975 Sep;1(3):277-299
references.pmid: 1235985
references.citation: J Med Genet. 1992 Dec;29(12):858-60
references.pmid: 1362221
references.citation: J Pain Symptom Manage. 2014 Jul;48(1):65-74
references.pmid: 24636960
references.citation: PLoS One. 2009 Jun 23;4(6):e6016
references.pmid: 19547755
references.citation: Genes Brain Behav. 2011 Jul;10(5):565-9
references.pmid: 21486391
references.citation: Mol Pain. 2006 Jul 18;2:24
references.pmid: 16848906
references.citation: Psychiatr Genet. 1996 Fall;6(3):131-3
references.pmid: 8902889
references.citation: Hematology Am Soc Hematol Educ Program. 2010;2010:403-8
references.pmid: 21239826
references.citation: J Pain. 2011 Aug;12(8):875-83
references.pmid: 21719351
references.citation: Am J Hum Biol. 2003 Sep-Oct;15(5):637-42
references.pmid: 12953175
references.citation: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references.pmid: 3344216
references.citation: Eur J Pain. 2005 Jun;9(3):229-32
references.pmid: 15862471
references.citation: Neuropsychopharmacology. 2004 Nov;29(11):1943-61
references.pmid: 15305167
references.citation: Expert Rev Neurother. 2008 May;8(5):781-97
references.pmid: 18457535
references.citation: Biol Psychiatry. 1996 Nov 15;40(10):1032-43
references.pmid: 8915563
references.citation: Cancer Nurs. 2011 May-Jun;34(3):228-37
references.pmid: 21512345
references.citation: Mol Psychiatry. 1998 Jul;3(4):333-6
references.pmid: 9702742
references.citation: Am J Hematol. 2010 Jan;85(1):29-35
references.pmid: 20029952
references.citation: Eur J Pain. 2013 Jan;17(1):16-27
references.pmid: 22528689
references.citation: Proc Natl Acad Sci U S A. 2011 Dec 20;108(51):20666-71
references.pmid: 22143780
references.citation: Ann Intern Med. 2008 Jan 15;148(2):94-101
references.pmid: 18195334
references.citation: PLoS One. 2013;8(1):e54108
references.pmid: 23365649
references.citation: Pain. 2011 Feb;152(2):300-307
references.pmid: 21130573
references.citation: J Clin Psychiatry. 2004;65 Suppl 12:16-9
references.pmid: 15315473
references.citation: PLoS One. 2011;6(11):e27764
references.pmid: 22132136
references.citation: Lancet. 1993 Apr 3;341(8849):906
references.pmid: 8096616
references.citation: Pain. 2006 Dec 5;125(3):216-224
references.pmid: 16837133
references.citation: Am J Hematol. 2005 May;79(1):17-25
references.pmid: 15849770
references.citation: N Engl J Med. 1991 Jul 4;325(1):11-6
references.pmid: 1710777
references.citation: Science. 2003 Feb 21;299(5610):1240-3
references.pmid: 12595695
references.citation: Biol Psychol. 2011 Apr;87(1):99-105
references.pmid: 21356266
references.citation: Pharmacogenet Genomics. 2012 Sep;22(9):673-91
references.pmid: 22722321
references.citation: Lancet. 2010 Dec 11;376(9757):2018-31
references.pmid: 21131035
references.citation: J Pain. 2009 Sep;10(9):969-75
references.pmid: 19464960
references.citation: Blood. 2012 Nov 1;120(18):3647-56
references.pmid: 22923496
references.citation: Mol Pain. 2008 Dec 18;4:64
references.pmid: 19094200
references.citation: Sleep Med Rev. 2013 Jun;17(3):173-83
references.pmid: 22748562
references.citation: Pain. 2009 Dec 15;147(1-3):187-93
references.pmid: 19796878
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 11;103(28):10753-8
references.pmid: 16809426