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.
METHODOLOGY: This study comprised of 249 participants (148 overweight/ obese as a case group and 101 lean participants as controls). The PCR-RFLP technique was performed to distinguish the genotype distribution of Leptin gene polymorphisms. The allele and genotype frequencies were assessed for single and haplotype analyses.
RESULT: Single association analysis of G2548A (P=0.74), A19G (P=0.38), and H1328080 (P=0.56) polymorphisms yielded no statistically significant association. However, haplotype association analysis showed a suggestive indication of AAG haplotype (G2548A, H1328080, and A19G sequence) with susceptibility effect towards obesity predisposition [P=0.002, OR=8.897 (1.59-9.78)].
CONCLUSION: This data on single and haplotype might disclose the preliminary exposure and pave the way for the obesity development with an evidence of revealed susceptibility to obesity.