Influence of catechol-O-methyltransferase (COMT) gene polymorphisms in pain sensibility of Brazilian fibromialgia patients

被引:53
作者
Barbosa, Flavia Regina [1 ]
Matsuda, Josie Budag [1 ]
Mazucato, Mendelson [2 ]
Franca, Suzelei de Castro [1 ]
Zingaretti, Sonia Marli [1 ]
da Silva, Lucienir Maria [3 ]
Martinez-Rossi, Nilce Maria [2 ]
Faria Junior, Milton [1 ]
Marins, Mozart [1 ]
Fachin, Ana Lucia [1 ]
机构
[1] Univ Ribeirao Preto, Unidade Biotecnol, BR-14096900 Ribeirao Preto, SP, Brazil
[2] Dept Genet FMRP USP, Ribeirao Preto, SP, Brazil
[3] Univ Ribeirao Preto, Hosp Electro Bonini, BR-14096900 Ribeirao Preto, SP, Brazil
关键词
Fibromyalgia; Genetic polymorphisms; Pain sensitive; FIQ; MORPHINE REQUIREMENTS; FIBROMYALGIA; PHARMACOGENETICS; VAL(158)MET; DISEASES;
D O I
10.1007/s00296-010-1659-z
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Fibromyalgia syndrome (FS) is a rheumatic syndrome affecting to 2-3% of individuals of productive age, mainly women. Neuroendocrine and genetic factors may play a significant role in development of the disease which is characterized by diffuse chronic pain and presence of tender points. Several studies have suggested an association between FS, especially pain sensitivity, and polymorphism of the catechol-O-methyltransferase (COMT) gene. The aim of the present study was to characterize the SNPs rs4680 and rs4818 of the COMT gene and assess its influence in pain sensitivity of patients with fibromyalgia screened by the Fibromyalgia Impact Questionnaire (FIQ). DNA was extracted from peripheral blood of 112 patients with fibromyalgia and 110 healthy individuals and was used as template in PCR for amplification of a 185-bp fragment of the COMT gene. The amplified fragment was sequenced for analyses of the SNPs rs4680 and rs4818. The frequency of mutant genotype AA of SNP rs6860 was 77.67% in patients with FS and 28.18% for the control group. For the SNP rs4818, the frequency of mutant genotype CC was 73.21 and 39.09% for patients with FS and controls, respectively. Moreover, the FIQ score was higher in patients with the homozygous mutant genotype for SNPs rs4680 (87.92 points) and rs4818 (86.14 points). These results suggest that SNPs rs4680 and rs4818 of the COMT gene may be associated with fibromyalgia and pain sensitivity in FS Brazilian patients.
引用
收藏
页码:427 / 430
页数:4
相关论文
共 34 条
[11]  
MARTINEZ JE, 1994, BRAZ J REUMATOL, V34, P309
[12]   Serotonin receptor (5-HT 2A) and catechol-O-methyltransferase (COMT) gene polymorphisms: Triggers of fibromyalgia? [J].
Matsuda, Josie Budag ;
Barbosa, Flavia Regina ;
Fernandes Morel, Lucas Junqueira ;
Franca, Suzelei de Castro ;
Zingaretti, Sonia Marli ;
da Silva, Lucienir Maria ;
Soares Pereira, Ana Maria ;
Marins, Mozart ;
Fachin, Ana Lucia .
REVISTA BRASILEIRA DE REUMATOLOGIA, 2010, 50 (02) :141-149
[13]   Pharmacogenetics - five decades of therapeutic lessons from genetic diversity [J].
Meyer, UA .
NATURE REVIEWS GENETICS, 2004, 5 (09) :669-676
[14]  
Nackley A G., 2005, COMT modulates pain sensitivity and cytokine production through both beta2 and beta3 adrenergic receptors
[15]   Low Enzymatic Activity Haplotypes of the Human Catechol-O-Methyltransferase Gene: Enrichment for Marker SNPs [J].
Nackley, Andrea G. ;
Shabalina, Svetlana A. ;
Lambert, Jason E. ;
Conrad, Mathew S. ;
Gibson, Dustin G. ;
Spiridonov, Alexey N. ;
Satterfield, Sarah K. ;
Diatchenko, Luda .
PLOS ONE, 2009, 4 (04)
[16]   Catechol-O-methyltransferase inhibition increases pain sensitivity through activation of both β2- and β3-adrenergic receptors [J].
Nackley, Andrea Gail ;
Tan, Kai Soo ;
Fecho, Karamarie ;
Flood, Patrick ;
Diatchenko, Luda ;
Maixner, William .
PAIN, 2007, 128 (03) :199-208
[17]  
Pinsonneault J, 2003, AAPS PHARMSCI, V5
[18]   Genetic variation in the Catechol-O-Methyltransferase (COMT) gene and morphine requirements in cancer patients with pain [J].
Rakvag, Trude T. ;
Ross, Joy R. ;
Sato, Hiroe ;
Skorpen, Frank ;
Kaasa, Stein ;
Klepstad, Pal .
MOLECULAR PAIN, 2008, 4
[19]   The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients [J].
Rakvåg, TT ;
Klepstad, P ;
Baar, C ;
Kvam, TM ;
Dale, O ;
Kaasa, S ;
Krokan, HE ;
Skorpen, F .
PAIN, 2005, 116 (1-2) :73-78
[20]   Pharmacogenetics and drug development: The path to safer and more effective drugs [J].
Roses, AD .
NATURE REVIEWS GENETICS, 2004, 5 (09) :645-656