Candidate-gene approach in fibromyalgia syndrome: Association analysis of the genes encoding substance P receptor, dopamine transporter and αl-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. Alphal -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. Eightyseven Jewish FMS patients participated; 45 of Ashkenazi origin, 32 of nonAshkettazi origin and 10 of unknown or mixed Jewish origin. Controls consisted of 200 healthy Jewish individuals. Genotyping of the 1354G >C allele inthe3'UTRofTACRl gene was performed by Ddel 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 candidategene approach study failed to identify significant associations between FMS and three genetic markers with hypothesis-driven clinical relevance. We suggest that a genomewide association study would be a more fruitful approach for further investigation of the genetic basis of FMS.