Candidate-gene approach in fibromyalgia syndrome: association analysis of the genes encoding substance P receptor, dopamine transporter and alpha1-antitrypsin.
BACKGROUND
Substance P receptor modulates stress, depression, anxiety and pain. Substance P is increased in CSF of fibromyalgia (FMS) patients. We examined the frequency of the substance P receptor (TACR1) 1354 G>C polymorphism in FMS.The dopamine transporter (DAT) SLC6A3 3' variable number tandem repeat (VNTR) polymorphism is associated with post traumatic stress disorder (PTSD), a condition with clinical and epidemiological overlap with FMS. We have evaluated the allele frequency of this polymorphism in FMS.Alpha1-antitrypsin (AAT) deficiency is an autosomal recessive metabolic disease. The PI ZZ phenotype, encoded by the E342K mutation, is associated with emphysema and liver disease, and has been linked with FMS. We have examined the frequency of this mutation in FMS.


METHODS
Eighty-seven Jewish FMS patients participated; 45 of Ashkenazi origin, 32 of non-Ashkenazi origin and 10 of unknown or mixed Jewish origin. Controls consisted of 200 healthy Jewish individuals. Genotyping of the 1354G >C allele in the 3' UTR of TACR1 gene was performed by DdeI restriction analysis, genotyping the SCL6A3 DAT 3' VNTR polymorphism was performed by PCR combined with GeneScan analysis, and the AAT E342K mutation was identified by TaqI restriction analysis.


RESULTS
No significant association was found between FMS and the three genetic markers studied here.


CONCLUSIONS
The current candidate-gene approach study failed to identify significant associations between FMS and three genetic markers with hypothesis-driven clinical relevance. We suggest that a genome-wide association study would be a more fruitful approach for further investigation of the genetic basis of FMS.
Ablin
J N
JN
Department of Rheumatology, Tel Aviv University, Israel. jacobab@tasmc.health.gov.il
Bar-Shira
A
A
Yaron
M
M
Orr-Urtreger
A
A
D000328:Adult; D000483:Alleles; D016009:Chi-Square Distribution; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005356:Fibromyalgia / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007557:Israel; D007585:Jews / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018040:Receptors, Neurokinin-1 / Q000235:genetics*; D000515:alpha 1-Antitrypsin / Q000235:genetics*
D050483:Dopamine Plasma Membrane Transport Proteins; D018040:Receptors, Neurokinin-1; C493214:SLC6A3 protein, human; D000515:alpha 1-Antitrypsin