Genetic variations in the serotonin 5-HT2A receptor gene (HTR2A) are associated with rheumatoid arthritis
- Anders Kling ( )
- Lisbeth Ärlestig ( )
- Lars Alfredsson ( )
- Leonid Padyukov ( )
- Published Online First 15 November 2007
Objectives: To analyse the association between the genetic polymorphisms within the HTR2A gene for the serotonin receptor and rheumatoid arthritis (RA).
Methods: The HTR2A gene polymorphisms were analysed in RA patients and controls from two study populations using PCR based restriction endonuclease mapping or TaqMan allelic discrimination with more than 4000 individuals included in the current study.
Results: At the discovery stage we detected significant differences in frequency of rs6313 (T102C polymorphism) between the RA patients and controls (p=0.006). Following validation with an extended set of single nucleotide polymorphisms (SNPs) and number of DNA samples a trend in associations in allelic model for SNPs rs6314, rs1328674, rs6313 and rs6311 (p=0.0064, 0.0021, 0.0060, 0.0088) was seen, although it was lost after correction for multi-comparison for all, but rs1328674 (empirical p-value=0.021). However, haplotype frequency analysis based on these four SNPs showed significantly low representation of TCTT combination in RA patients in comparison with controls (3.6% and 5.6%, p=0.0004 in Chi-square test, empirical p=0.0038 after 100,000 permutations) and a significantly higher frequency of CTCC combination in RA patients in comparison with controls (3.6% and 2.2%, p=0.0022 in Chi-square test, empirical p=0.0217 after 100,000 permutations).
Conclusions: In our study, genetic polymorphisms at HTR2A gene are associated with susceptibility for RA suggesting possible links between the serotonergic system and development of the disease.