Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains

Abstract

Objective. Fibromyalgia (FM) patients have signs of relentless sympathetic hyperactivity associated with hyporeactivity to stress. Adrenergic receptors (ARs) are parts of the sympathetic nervous system that are fundamental for maintenance of homeostasis. We undertook this study to correlate ␣-AR and ␤-AR gene polymorphisms with the presence of FM and with different domains of the FM syndrome as measured by the Fibromyalgia Impact Questionnaire (FIQ).Methods. We studied 78 Mexican FM patients and 48 age-matched controls as well as 78 Spanish FM patients and 71 controls. All subjects studied were women. Single-nucleotide polymorphisms (SNPs) of ␣ 1A -AR (rs574584, rs1383914, rs1048101, and rs573542), ␤ 2 -AR (rs1042713 and rs1042714), and ␤ 3 -AR (rs4994) were analyzed by 5 exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis.Results. The ␤ 2 -AR AC haplotype was a risk factor for the presence of FM. This haplotype had an increased frequency in Mexican patients compared with Mexican controls (42.1% versus 30.5%; P ‫؍‬ 0.04). Similarly, 50.4% of Spanish patients had this haplotype compared with 40.0% of Spanish controls (P ‫؍‬ 0.05). In Spanish patients, the ␣ 1A -AR SNP rs1383914 was associated with the presence of FM (P ‫؍‬ 0.01), and the ␣ 1A -AR SNP rs1048101 was linked with FIQ disability (P ‫؍‬ 0.02). Mexican patients with the rs574584 GG genotype presented the highest FIQ score compared with Mexican patients with other genotypes (P ‫؍‬ 0.01), and in Mexicans SNP rs574584 was associated with FIQ morning stiffness (P ‫؍‬ 0.04) and with FIQ tiredness upon awakening (P ‫؍‬ 0.02).Conclusion. AR gene polymorphisms are related to the risk of developing FM and are also linked to different domains of the FM syndrome.

Candidate gene studies of fibromyalgia: a systematic review and meta-analysis

“…Significant familial aggregation, convincing demonstrations of genetic linkages and associations demonstrate an underlying genetic basis for fibromyalgia [5]. Many studies have examined the potential contribution of the candidate gene polymorphisms to fibromyalgia susceptibility, but these studies have produced diverse results [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23].…”

Effects of Bedtime Very Low Dose Cyclobenzaprine on Symptoms and Sleep Physiology in Patients with Fibromyalgia Syndrome: A Double-blind Randomized Placebo-controlled Study

“…We recently reported that CBP is a potent inhibitor of 5-HT2a and the adrenergic a-2 receptors -A, -B, and -C 37 . Genetic linkages have associated FM with genes encoding 5-HT2a and adrenergic receptors 38,39 . In addition, ritanserin, another 5-HT2a receptor inhibitor, provided benefit to the sleep quality but not to pain or tenderness of patients with FM 40 .…”

DNA Testing Applied to Fibromyalgia Syndrome Analysis and Management

“…also included in our study as well as polymorphisms at adrenergic receptor genes, 23 and special immunogenetics leading to a proinflammatory status, [16][17][18]34 among others as CYP450 enzymatic polymorphisms which are mainly related to the pain management. [35][36][37][38] All these genes are involved in the neurotransmitters balance determining the potential to have excess or defect in any of them.…”