Association between CTLA-4 polymorphisms and the susceptibility to systemic lupus erythematosus and Graves’disease in Thai population.

Background: Cytotoxic T-lymphocyte antigen-4 (CTLA-4) is a cell surface molecule involved in the regulation of T cells. Single nucleotide polymorphisms (SNPs) of CTLA-4 gene are known to be associated with susceptibility to several autoimmune diseases, including systemic lupus erythematosus (SLE) and Graves’ disease (GD). Objective: The aim of this study was to determine whether the common SNPs +49A/G on exon1 and CT60A/G in 3’UTR of the CTLA-4 gene are associated with susceptibility to SLE and GD in Thai population. Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze these two SNPs in 151 patients with SLE, 132 patients with GD and 153 healthy controls. Results: Our study showed that there were no statistically significant differences in the allele and genotype frequencies of +49A/G and CT60A/G SNPs between patients with SLE and healthy controls as well as patients with GD vs. healthy controls (P >0.05). However, the GG genotypes of +49A/G and CT60A/G were likely to be risk factors (OR >1) for GD but not in SLE. The effect of the +49G allele was similar to that of an autosomal recessive gene in the presence of the GG genotype, when compared to AA and AG, with an OR of 1.58 (95% CI =0.95-2.61, p =0.061) in GD. We also observed a dose response effect of the CT60G allele on GD susceptibility with an OR of 1.43 for GG homozygous and 1.17 for AG heterozygous subjects, when compared to the AA genotype, although these were not statistically significant (P >0.05). Conclusion: We found no association between two functional polymorphisms (+49A/G and CT60A/G) of the CTLA-4 gene and susceptibility to SLE and GD. However, the association study utilizing a larger sample size should be performed to confirm this.

Distribution of human leukocyte antigens-E alleles in Thailand.

The aim of this study was to investigate the distribution of human leukocyte antigens (HLA) -E alleles in Thailand. HLA-E alleles were assigned by using a polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method and direct sequencing in 200 healthy individuals. They comprised 100 Thai, 50 Chinese and 50 Thai-Chinese. From the results, three alleles of HLA-E could be detected in these populations. The E*0101 was the most common allele in Thai and Thai-Chinese with allelic frequencies of 42.5 per cent and 38 per cent, respectively. The other HLA-E allele frequencies of Thai origin were 33 per cent for E*01031 and 24.5 per cent for E*01032, respectively. Among Thai-Chinese, the allele frequencies of HLA-E were 31 per cent for E*01031 and E*01032, respectively. Whereas, the E*01031 was the predominant allele in Chinese origin with a frequency of 39 per cent, followed by E*0101 and E*01032 with 32 per cent and 29 per cent, respectively. No E*01033, E*0102 and E*0104 could be detected in all individuals. When comparing the distribution of HLA-E alleles between each of the populations (Thai vs Chinese, Thai vs Thai-Chinese and Chinese vs Thai-Chinese), no significant difference could be found among these populations. In addition, there was no significant difference of the distribution of HLA-E alleles between the study populations and other populations from Asian countries, reported previously. However, there were significant differences between the populations (Thai, Chinese and Thai-Chinese) and Danish (chi2 = 15.64, p = 0.0004; chi2 = 24.58, p = 0.0000046; chi2 = 14.69, p = 0.00065, respectively).

DRB1*04 subtype in Thai patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) in a Thai population is significantly associated with HLA-DR4. The frequency of DR4 was 43 per cent in RA patients and 20 per cent in the healthy controls (p = 0.00008, OR = 3.06, 95% CI = 1.71, 5.52). To analyze which DR4 alleles were associated with the disease, the authors subtyped 52 DR4-positive RA patients compared to 28 DR4-positive healthy controls by amplification with DR4-specific primers followed by direct sequencing. Six DR4 alleles (DRB1*0401, *0403, *0404, *0405, *0406, and *0410) were found in the RA patient group while 5 alleles (DRB1*0401, *0403, *0405, *0406, and *0407) were found in the control group. Both groups were predominated by DRB11*0405, but there was a significant increase in the frequency of DRB1*0405 in DR4+ RA patients compared to DR4+ healthy controls (84.6% vs 46.4%, p = 0.0008, OR = 6.35, 95% CI = 1.96, 21.08). DR4 which shared epitope alleles (DRB1*0401, *0404, *0405) were observed in 47 (90.3%) DR4+ patients and 15 (53.5%) DR4+ controls (p = 0.0005, OR = 8.15, 95% CI = 2.29, 33.2). In addition, the authors found that DRB1*0403 was significantly decreased in DR4+ RA patients compared to controls (p = 0.0065, OR = 0.07, 95% CI = 0, 0.67).