Association of adrenergic receptor gene polymorphisms with different fibromyalgia syndrome domains.
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 alpha-AR and beta-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 alpha(1A)-AR (rs574584, rs1383914, rs1048101, and rs573542), beta(2)-AR (rs1042713 and rs1042714), and beta(3)-AR (rs4994) were analyzed by 5' exonuclease TaqMan polymerase chain reaction. Polymorphic haplotypes were constructed after linkage disequilibrium analysis.


RESULTS
The beta(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 alpha(1A)-AR SNP rs1383914 was associated with the presence of FM (P = 0.01), and the alpha(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).


CONCLUSIONS
AR gene polymorphisms are related to the risk of developing FM and are also linked to different domains of the FM syndrome.
Vargas-Alarcón
Gilberto
G
National Institute of Cardiology Ignacio Chávez, Tlalpan, Mexico City, Mexico.
Fragoso
José-Manuel
JM
Cruz-Robles
David
D
Vargas
Angélica
A
Martinez
Aline
A
Lao-Villadóniga
José-Ignacio
JI
García-Fructuoso
Ferrán
F
Vallejo
Maite
M
Martínez-Lavín
Manuel
M
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005356:Fibromyalgia / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006306:Health Surveys; D006801:Humans; D008800:Mexico; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics*; D018340:Receptors, Adrenergic, alpha-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics*; D012307:Risk Factors; D013030:Spain; D013577:Syndrome
C547713:ADRA1A protein, human; D018340:Receptors, Adrenergic, alpha-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3