Association of tri-nucleotide (CAG and GGC) repeat polymorphism of androgen receptor gene in Taiwanese women with refractory or remission rheumatoid arthritis

Abstract

We investigated the relationship between CAG and GGC repeat polymorphism of the androgen receptor (AR) gene and rheumatoid arthritis (RA) in female patients with different disease subtypes. This case-control study enrolled 215 women in three groups: RA patients refractory to standardized therapy (n = 51); RA patients at complete remission phase (n = 60); and healthy controls (n = 104). CAG and GGC repeat lengths were determined by automated fluorescence-based DNA fragment-sizing method. Demographic data, allele lengths, allele distribution, and zygosity status of CAG/GGC repeats were assessed for the three groups. Refractory RA patients tend to have a significantly younger onset age of RA and more elevated erythrocyte sedimentation rates than do remission RA patients. Mean and median values of CAG and GGC repeat lengths are similar in both RA and control patients. However, RA patients harboring any long CAG alleles with more than 23 repeats had an increased risk of a refractory course, whereas differences in risk were not observed between these patients and RA subtypes harboring any long GGC alleles with more than 16 repeats. In addition, the homozygous frequency of CAG but not GGC alleles was lower in refractory RA than in remission RA patients or in controls (p = 0.042). Neither CAG nor GGC repeat lengths had a significant relationship with rheumatoid factor reactivity. Our observations indicate that short CAG repeats of the AR gene with higher transactivation activity may have protective effects against refractory course of RA development and that homozygous frequency of CAG alleles may be involved in the disease remission subtype. In contrast, lack of association of GGC polymorphism and RA was also observed. Together, these data imply that CAG but not GGC alleles in the AR polymorphism may play an important role in modulating the disease pattern of RA among Taiwanese women.

Androgen receptor genetic variants in male patients with ankylosing spondylitis in Taiwan

“…For association analysis, we split the samples into high repeat and low repeat groups, based on the mean and median of repeat numbers as the cut-off and on previous published results. 25,35 The number of CAG repeats 21 did not differ in the AS cases and healthy controls. The International Journal of Rheumatic Diseases 2013; 16: 81-87 same findings were observed for cut-off points at 22 or 23 repeats (data not shown).…”

“…As shown in Figure 1, the distribution of CAG or GGC repeats was approximately normal for the AS cases and controls, and was similar to that obtained in our previous study. 25 The mean and median number of CAG repeats did not differ significantly between the AS cases and controls. For association analysis, we split the samples into high repeat and low repeat groups, based on the mean and median of repeat numbers as the cut-off and on previous published results.…”

“…The determination of CAG and GGC repeats in the AR gene has been reported previously. 25 In brief, we genotyped CAG and GGC repeats with an ABI 3100 82 International Journal of Rheumatic Diseases 2013; 16: 81-87 sequencer (Applied Biosystems, Foster City, CA, USA) using the fluorescence-based DNA fragment-sizing method. Five single nucleotide polymorphisms (SNPs) in the AR gene (rs962458, rs6152, rs1204038, rs2361634, rs1337080) were selected because of the significant associations found in previous studies.…”

“…The length of the CAG and GGC repeats in the AR gene is inversely correlated with the transactivation function of AR. [22][23][24] The CAG-repeat polymorphism in the AR gene has been shown to be a significant risk factor for several gender-specific autoimmune diseases, such as RA in a Taiwanese population 25 and AS in a Japanese population. 26 Shorter CAG repeats of the AR gene, presenting high levels of transactivation activity, may play a role in male AS.…”

Lack of association between CAG repeat polymorphism in the androgen receptor gene and the outcome of rheumatoid arthritis treatment with leflunomide

“…Only one study examined the association between CAG polymorphism of the AR gene and response to therapy in RA. Patients harboring long CAG alleles with >23 repeats had an increased risk of a worse response to DMARDs, but it was not shown how many patients were treated with LEF [27]. …”