METHODS: We conducted a cross-sectional study from July to October 2019 that included all patients with gout who attended the clinics. Data on clinical demographics and laboratory results were collected. Comparison between tophaceous and non-tophaceous groups was performed using descriptive analysis.
RESULTS: A total of 421 patients with gout were involved in this study, 83 (19.7%) patients had visible tophi and were categorized into the tophaceous group, while the other 338 (80.3%) patients were categorized into the non-tophaceous group. The majority of patients were male with a mean age of 57.6±12.8 years. Three factors found to be significantly associated with tophaceous gout were age at symptom onset [tophaceous (45.6±13.3 years) vs. non-tophaceous (49.7±13.9 years), p = 0.026], mean disease duration of gout [tophaceous (105.2±92.6 months) vs. non-tophaceous (77.6±88.6 months), p = 0.013], and baseline serum uric acid level [tophaceous (622.3±129.1 µmol/L) vs. non-tophaceous (582.6±102.3 µmol/L), p = 0.021].
CONCLUSIONS: Tophaceous gout is associated with longer disease duration, higher baseline serum uric acid level, and younger age at symptoms onset. Hence, early initiation of urate-lowering therapy with a treat-to-target approach is crucial to prevent tophi formation.
METHODS: We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region.
RESULTS: We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30-5.49, PGWAS = 7.22 × 10-29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37-0.62, PGWAS = 2.58 × 10-08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09-0.30, PGWAS = 1.60 × 10-09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia.
CONCLUSIONS: Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.