PMID- 18267980 OWN - NLM STAT- MEDLINE DCOM- 20081215 LR - 20111117 IS - 1468-2060 (Electronic) IS - 0003-4967 (Linking) VI - 67 IP - 12 DP - 2008 Dec TI - Association between beta2 adrenergic receptor polymorphisms and rheumatoid arthritis in conjunction with human leukocyte antigen (HLA)-DRB1 shared epitope. PG - 1759-64 LID - 10.1136/ard.2007.083782 [doi] AB - OBJECTIVE: In the present work, the frequency of inherited polymorphisms of the beta2 adrenergic receptor (beta2AR) gene and their association with rheumatoid arthritis (RA) as well as human leukocyte antigen (HLA)-DRB1 alleles was examined. METHODS: An allele-specific polymerase chain reaction was used to determine the common variants of the beta2AR at positions 16, 27 and 164 in patients with RA (n=310) and ethnically matched healthy controls (n=305) from Germany. HLA-DRB1 genotyping was performed by oligonucleotide hybridisation of enzymatically amplified DNA allowing low-resolution HLA-DRB1 genotyping comprising specificities DRB1*01 to DRB1*17. RESULTS: Arginine (Arg) at codon 16 was present in 278 patients with RA (89.7%) compared to 202 controls (66.2%; odds ratio (OR) 4.43, 95% CI 2.81 to 7.02, p<0.001). Homozygosity for Arg16 was found in 107 patients with RA (34.5%) compared to 14 controls (4.6%; OR 10.9, CI 5.9 to 20.5, p<0.001). Stratifying patients for their HLA-DR status revealed that homozygosity for Arg16 exhibited the greatest risk for RA in combination with HLA-DRB1*04 (OR 17.1, 95% CI 1.71 to 414.4, p=0.004). Interestingly, patients with the Arg16 allele have a younger mean (SD) age at disease onset compared to patients without Arg16 (46.1 (2.0) vs 53.1 (2.7) respectively, p<0.05). Furthermore, 93.3% patients with homozygosity for Arg16 were positive for anti-cyclic citrullinated peptide (CCP) antibodies vs 75% patients with homozygosity for Gly16 (p<0.05). CONCLUSION: There was a highly significant distortion between patients with RA and controls in the distribution of beta2AR polymorphisms at codon 16, contributing (together with the HLA-DR alleles) to the genetic background of RA. FAU - Malysheva, O AU - Malysheva O AD - Medical Clinic IV, University Hospital, Liebigstrasse 22, 04103 Leipzig Germany. Olga.Malysheva@medizin.uni-leipzig.de FAU - Pierer, M AU - Pierer M FAU - Wagner, U AU - Wagner U FAU - Wahle, M AU - Wahle M FAU - Wagner, U AU - Wagner U FAU - Baerwald, C G AU - Baerwald CG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080211 PL - England TA - Ann Rheum Dis JT - Annals of the rheumatic diseases JID - 0372355 RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DRB1 Chains) RN - 0 (Receptors, Adrenergic, beta-2) SB - IM MH - Adult MH - Arthritis, Rheumatoid/*genetics MH - Case-Control Studies MH - Female MH - Gene Frequency MH - Genetic Predisposition to Disease MH - Genotype MH - HLA-DR Antigens/*genetics MH - HLA-DRB1 Chains MH - Heterozygote MH - Humans MH - Male MH - Middle Aged MH - Polymerase Chain Reaction/methods MH - *Polymorphism, Genetic MH - Receptors, Adrenergic, beta-2/*genetics MH - Severity of Illness Index EDAT- 2008/02/13 09:00 MHDA- 2008/12/17 09:00 CRDT- 2008/02/13 09:00 PHST- 2008/02/13 09:00 [pubmed] PHST- 2008/12/17 09:00 [medline] PHST- 2008/02/13 09:00 [entrez] AID - ard.2007.083782 [pii] AID - 10.1136/ard.2007.083782 [doi] PST - ppublish SO - Ann Rheum Dis. 2008 Dec;67(12):1759-64. doi: 10.1136/ard.2007.083782. Epub 2008 Feb 11.