OBJECTIVES: To analyse the association between the genetic polymorphisms within the HTR2A gene for the serotonin receptor and rheumatoid arthritis (RA). METHODS: HTR2A gene polymorphisms were analysed in patients with RA 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 patients with RA 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 = 0.006, 0.002, 0.006, 0.009) 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 patients with RA in comparison with controls (3.6% and 5.6%, p<0.001 on chi(2) test, empirical p = 0.004 after 100 000 permutations) and a significantly higher frequency of CTCC combination in patients with RA in comparison with controls (3.6% and 2.2%, p = 0.002 on chi(2) test, empirical p = 0.022 after 100 000 permutations). CONCLUSIONS: In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease.
OBJECTIVES: To analyse the association between the genetic polymorphisms within the HTR2A gene for the serotonin receptor and rheumatoid arthritis (RA). METHODS:HTR2A gene polymorphisms were analysed in patients with RA 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 patients with RA 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 = 0.006, 0.002, 0.006, 0.009) 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 patients with RA in comparison with controls (3.6% and 5.6%, p<0.001 on chi(2) test, empirical p = 0.004 after 100 000 permutations) and a significantly higher frequency of CTCC combination in patients with RA in comparison with controls (3.6% and 2.2%, p = 0.002 on chi(2) test, empirical p = 0.022 after 100 000 permutations). CONCLUSIONS: In our study, genetic polymorphisms at the HTR2A gene are associated with susceptibility for RA, suggesting possible links between the serotonergic system and development of the disease.
Authors: Maria Seddighzadeh; Marina Korotkova; Henrik Källberg; Bo Ding; Nina Daha; Fina A S Kurreeman; Rene E M Toes; Tom W Huizinga; Anca I Catrina; Lars Alfredsson; Lars Klareskog; Leonid Padyukov Journal: Eur J Hum Genet Date: 2010-02-24 Impact factor: 4.246
Authors: Ryan M Smith; Audrey C Papp; Amy Webb; Cara L Ruble; Leanne M Munsie; Laura K Nisenbaum; Joel E Kleinman; Barbara K Lipska; Wolfgang Sadee Journal: Biol Psychiatry Date: 2012-11-13 Impact factor: 13.382
Authors: Samina Asad; Pernilla Nikamo; Alexandra Gyllenberg; Hedvig Bennet; Ola Hansson; Nils Wierup; Annelie Carlsson; Gun Forsander; Sten-Anders Ivarsson; Helena Larsson; Åke Lernmark; Bengt Lindblad; Johnny Ludvigsson; Claude Marcus; Kjersti S Rønningen; Jan Nerup; Flemming Pociot; Holger Luthman; Malin Fex; Ingrid Kockum Journal: PLoS One Date: 2012-05-01 Impact factor: 3.240