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Fc gamma receptor gene variants associated with rheumatoid arthritis

April 01, 2017

A study published today in the journal Arthritis Research & Therapy confirms previous findings of an association between the Fc gamma Receptor (FCGR) gene family and rheumatoid arthritis (RA). The study shows that a specific variant combination of two FCGR genes on chromosome one, a FCGR3A-FCGR3B haplotype, makes people more susceptible to RA.

Ann Morgan, from the University of Leeds, and colleagues from other institutions in the UK studied the frequency of various FCGR haplotypes in a group of UK Caucasians (147 RA patients and 127 healthy individuals acting as controls). Dr Morgan is an Arthritis Research Campaign ???Clinician Scientist Fellow??.

One specific FCGR3A-FCGR3B haplotype was found in 31% of RA patients and in 37% of RA patients with a more severe type of RA characterised by lumps around the joints, or nodules. Individuals with 2 copies of this haplotype (homozygous) are three times more likely to develop RA. Homozygous individuals who also have certain variants of human leukocyte antigen (HLA)-DRB1 alleles encoding the ???shared epitope?? protein sequence (SE positive), a known risk factor for RA, have a 10 times higher risk of developing RA than SE negative individuals with other FCGR3 variants.

The Fc gamma receptors play important roles in the initiation and regulation of many immunological and inflammatory processes. They also have the ability to bind RA-associated antibodies. This might explain their role in RA pathogenesis.

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4.24 for more than 200 mg/day of celecoxib 5.03 for more than 25 mg/day of rofecoxib 3.76 for more than 100 mg/day of diclofenac 1.22 for other NSAIDs (other non-specified NSAIDs were not divided into high or low dosages because it was a very heterogeneous group) 1.96 for more than 1200 mg/day of ibuprofen

Lower doses of celecoxib (hazard ratio 1.70) and rofecoxib (2.23) were also associated with a significantly higher risk of death, which was not found with lower doses of ibuprofen (hazard ratio 0.66) or diclofenac (0.74).

"The most important thing to recognize is that higher doses give a higher risk of death," Gislason said.

However, researchers did not find an increased risk of a second heart attack with any of the drugs or dosages. "This really surprised us because we had expected that the risk of recurrent heart attack would be high in this population," Gislason said.

The research team is analyzing death certificates to see what (if any) causes of death were more common in patients taking the drugs. "We're looking at both cardiovascular and non-cardiovascular causes of death," Gislason stated.

Gislason recommends that patients with cardiovascular disease who are taking COX-2 inhibitors or other NSAIDs should talk to their doctors.

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