Polymorphisms of Adrenergic Cardiovascular Control Genes are Associated with Adolescent Chronic Fatigue Syndrome

Abstract

Background Chronic fatigue syndrome (CFS) is characterized by alterations of adrenergic cardiovascular regulation. We explored the presence of polymorphisms in adrenergic cardiovascular control genes in adolescent with CFS, and their relation to cardiovascular variables.

Methods DNA from 52 CFS patients were analysed for 5 single nucleotide polymorphisms (SNPs) in genes encoding the Catechol-O-methyltransferase (COMT) (rs4680), the beta2-adrenergic receptor (rs1042713, rs1042714), the beta1-adrenergic receptor (rs1801253) and the alpha2a-adrenergic receptor (rs1800544). Frequencies were compared to a reference population constructed from the NCBI database. Furthermore, associations between autonomic cardiovascular responses during a 20 degrees head-up tilt-test and polymorphisms frequencies within the patient group were explored.

Results For the COMT SNP at rs4680, CFS patients had a higher frequency of the AA genotype (Met/Met) and a lower frequency of the G (Val) containing genotypes (AG and GG), as compared to the reference sample (p=0.046). Also, among CFS patients, the AA genotype was associated with lower diastolic blood pressure (DBP) at baseline (p=0.028) and a smaller increase in LF/HF (and index of cardiac sympathovagal balance) during head-up tilt (p=0.045) as compared to the AG/GG genotypes. For the rs1042714 SNP in the beta2-adrenergic receptor gene, CFS patients had a lower frequency of the GG genotype and a higher frequency of the genotypes containing C (CG and CC) (p=0.044). No associations to cardiovascular variables were found.

Conclusion Genetic susceptibility to CFS might be related to polymorphisms of COMT and the beta2-adrenergic receptor. The importance of polymorphisms in other adrenergic cardiovascular control genes should be explored in further studies.