Search

Studies have shown that the genetic risk factors for rheumatoid arthritis (RA) differ substantially between Asian and Caucasian populations. Even among Asian populations, the genetic contributions of NLRP1, PTPN22 and PADI4 have been controversial. Consequently, we sought to address these separate findings and determine whether any of these proposed risk variants are associated with RA susceptibility, onset, DAS activity and erosion in a Singaporean Chinese cohort. We genotyped five SNPs within NLRP1 (rs878329 and rs6502867), PTPN22 (rs2488457 and rs6665194), and PADI4 (rs2240340) in 500 anti-cyclic citrullinated peptide antibody-positive (ACPA) patients with RA and 500 healthy controls using TaqMan assays. The CC genotype of NLRP1 rs878329 and TT genotype of PADI4 rs2240340 were associated with RA susceptibility. The risk association of the T allele of PADI4 rs2240340 with RA was confirmed through a meta-analysis based on previous reports in Asian populations. The GG genotype of PTPN22 rs6665194 (-3508A>G) was associated with significantly reduced risk of RA. No significant association was found for NLRP1 rs6502867 T/C and PTPN22 rs2488457 G/C polymorphisms. None of the five SNPs was associated with RA's clinical features. This work supports the association of the T allele of PADI4 rs2240340 with RA in Asians. The roles of NLRP1 rs878329 G/C and PTPN22 rs6665194 A/G polymorphisms were demonstrated for the first time. We also propose rs6665194 to be a promising candidate for RA risk evaluation between ethnicities.

Background: Genetic determinants of drug response remain stable throughout life and offer great promise to patient-tailored drug therapy. The adoption of pharmacogenetic (PGx) testing in patient care requires accurate, cost effective and rapid genotyping with clear guidance on the use of the results. Hence, we evaluated a 32 SNPs panel for implementing PGx testing in clinical laboratories., Methods: We designed a 32-SNP panel for PGx testing in clinical laboratories. The variants were selected using the clinical annotations of the Pharmacogenomics Knowledgebase (PharmGKB) and include polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A5 and VKORC1 genes. The CYP2D6 gene allele quantification was determined simultaneously with TaqMan copy number assays targeting intron 2 and exon 9 regions. The genotyping results showed high call rate accuracy according to concordance with genotypes identified by independent analyses on Sequenome massarray and droplet digital PCR. Furthermore, 506 genomic samples across three major ethnic groups of Singapore (Malay, Indian and Chinese) were analysed on our workflow., Results: We found that 98% of our study subjects carry one or more CPIC actionable variants. The major alleles detected include CYP2C9*3, CYP2C19*2, CYP2D6*10, CYP2D6*36, CYP2D6*41, CYP3A5*3 and VKORC1*2. These translate into a high percentage of intermediate (IM) and poor metabolizer (PM) phenotypes for these genes in our population., Conclusion: Genotyping may be useful to identify patients who are prone to drug toxicity with standard doses of drug therapy in our population. The simplicity and robustness of this PGx panel is highly suitable for use in a clinical laboratory., Competing Interests: The authors have declared that no competing interests exist.

Objective: We have previously validated the English version of the Systemic Lupus Erythematosus Quality of Life Questionnaire (SLEQOL) in our patients with lupus. Many of our Chinese patients are not fluent in English and therefore a Chinese version (SLEQOL-C) has been adapted for their use., Methods: Two independent translators translated the SLEQOL into Chinese. A consensus version was derived from both sets of translations. Back translation of this version was performed by another 2 independent translators who had neither been involved in the forward translation nor encountered the SLEQOL. The final version, SLEQOL-C, was finalized after rectifying the discrepancies revealed by the back translation. Linguistic validity was tested in open interviews with bilingual patients with lupus. The SLEQOL-C and SLEQOL were administered to patients to determine whether they displayed differential item functioning (DIF)., Results: In general, most of the items in English could be expressed in Chinese precisely, although a few instructions had to be altered slightly to make them more idiomatic. The forward and back translations of the SLEQOL were accomplished without major difficulties. A total of 638 patients were interviewed (62.8% with the SLEQOL and 37.2% with the SLEQOL-C). Using DIF analysis, there was no detectable test bias due to language use after controlling for repeated observations, age, sex, and ethnicity., Conclusion: The SLEQOL-C has semantic, idiomatic, and conceptual equivalence to the SLEQOL. The rigorous process of cross-cultural translation provides some measure of quality in the content validity.