Polymorphisms of adrenergic cardiovascular control genes are associated with adolescent chronic fatigue syndrome

Aim: To explore the frequency of polymorphisms in adrenergic cardiovascular control genes in adolescent with chronic fatigue syndrome (CFS) and the relation of such polymorphisms to cardiovascular variables. Methods: DNA from 53 patients with CFS, 12-18 years old, was analysed for five single nucleotide polymorphisms (SNPs) in the genes catechol-O-methyltransferase (COMT), the beta(2)-adrenergic receptor (two SNPs), the beta(1)-adrenergic receptor and the alpha(2a)-adrenergic receptor. Frequencies were compared to a reference population constructed from the National Center for Biotechnology Information (NCBI) database, and associations between frequencies and autonomic cardiovascular responses during a 20 degrees head-up tilt-test were explored. Results: For the COMT SNP Rs4680, patients with CFS had a higher frequency of the AA genotype and a lower frequency of the G containing genotypes (AG and GG), when compared to the reference sample (p = 0.046). Also, the AA genotype was associated with a smaller increase in LF/HF ratio (low-frequency: high-frequency heart rate variability ratio, an index of cardiac sympathovagal balance) during head-up tilt when compared to the AG/GG genotypes. For the beta(2)-adrenergic receptor SNP Rs1042714, patients with CFS had a lower frequency of the GG genotype and a higher frequency of the genotypes containing C (CG and CC) (p = 0.044). Conclusions: CFS might be related to polymorphisms of COMT and the b2-adrenergic receptor. More details of the molecular mechanisms remain to be investigated.