Association of HLA-DRB1*15:02 and DRB5*01:02 allele with the susceptibility to systemic sclerosis in Thai patients.

A genetic study, particularly in HLA-DRs, has never been performed in Thai patients with systemic sclerosis (SSc). This study was performed to investigate the association between the HLA-DR series in Thai SSc patients. HLA-DR subtypes were determined in 50 Thai SSc patients and 99 healthy controls (HCs). All SSc patients met the ACR classification criteria for SSc. HLA-DR typing was performed using INNO-LiPA HLA-DRB Decoder kits (INNOGENETICS) and reconfirmed using MICRO SSP HLA DNA Typing kits (ONE LAMBDA). The allele frequency (AF) of HLA-DR*15, compared with HC, was significantly higher in all SSc patients (41.0 vs 21.7%, Pc = 0.0083) and SSc patients with anti-Scl70 antibody positive (anti-Scl70+) (47.1%, Pc = 0.0018). Among the HLA-DR*15 alleles, the AF of the DRB1*15:02 was increased significantly in all SSc patients (29.0 vs 12.6%, Pc = 0.0219) and SSc patients with anti-Scl70+ (32.4 vs 12.6%, Pc = 0.0196). The AF of the HLA-DRB5*01:02 allele was also increased in all SSc patients (27.0 vs 12.6%, Pc = 0.0166) and in SSc patients with anti-Scl70+ (29.4%, Pc = 0.0124). The AF of the DR*04 was significantly lower in the SSc patients (1.0 vs 9.6%, Pc = 0.0399). However, the AF of the DRB1*15:02 and DRB5*01:02 was not different among SSc patients with or without clinical manifestations (pulmonary fibrosis, digital pitting scar, sclerodactyly, myositis, and sicca symptoms). In addition, there was no significant association between clinical manifestations among individuals who carried HLA-DRB1*15:02 or DRB5*01:02. HLA-DRB1*15:02 and DRB5*01:02 alleles were significantly elevated in Thai SSc patients, especially in those with anti-Scl70+. The HLA-DRB1*04 was a protective allele against Thai SSc patients.

Lack of CTGF*-945C/G Dimorphism in Thai Patients with Systemic Sclerosis.

An association between connective tissue growth factor (CTGF) gene dimorphism at -945 (CTGF*-945C/G) and systemic sclerosis (SSc) has been reported with inconclusive results. We performed this study to determine whether such an association exists among Thai patients with SSc. DNA samples were taken from 50 Thai SSc patients (diffuse SSc in 39 and limited SSc in 11) and 99 healthy controls for determination of CTGF*-945C/G dimorphism by polymerase chain reaction (PCR) using specific oligonucleotide primers. The associations between the genotype frequencies, clinical manifestations and auto-antibodies were determined as well. When compared with the controls, SSc patients had no significantly higher frequencies of the GG genotype (44.0% vs 39.4%, p = 0.60), G allele (63.0% vs 65.2%, p = 0.80) or G phenotype (82.0% vs 90.9%, p = 1.0). There was no association between the presence of the GG genotype and clinical manifestations (pulmonary fibrosis, sclerodactyly, digital pitting scars, telangiectasia and pulmonary arterial hypertension), or the presence of auto-antibodies (anti-Scl-70, anti-SSA/Ro, and anti-RNP). In conclusion, we found no association between CTGF*-945C/G dimorphism and Thai SSc patients.

Genetic association of HLA-A*2601 with ocular Behçet's disease in Japanese patients.

OBJECTIVES: Behçet's disease (BD) is known to be associated with HLA-B*51, especially HLA-B*5101, in many different ethnic groups. Recently, several HLA-A or -B alleles have been proposed as possible candidate genes for BD in addition to HLA-B*5101. To investigate those associations, we studied HLA-A and -B alleles in Japanese ocular BD patients and the association of possible susceptibility HLA genes with visual prognosis. METHODS: Eighty-eight Japanese BD patients with uveitis and 104 healthy controls were enrolled for analyses of HLA-A and B alleles. Statistical analysis was performed with Fisher's exact test and odds ratio (OR). Association of the possible susceptible HLA gene and visual prognosis was also examined. RESULTS: The phenotype frequency (PF) of HLA-A*2601 was significantly higher in the patients (37.5%) than the controls (14.4%) (pc=0.00529, OR=3.56), especially in patients without HLA-B*5101 (57.4% vs. 14.1%, pc=4.58x10-6, OR=8.21). In contrast, the PF of HLA-A*2601 was not increased in patients with HLA-B*5101 (14.6% vs. 15.8%). Also, the PF in patients possessing HLA-A*2601 or HLAB* 5101 was increased up to 77.3%. Interestingly, the PF of HLA-A*2601 was significantly associated with poor visual prognosis corresponding to visual acuity of 0.1 or less in the worse eye (p=0.0262). CONCLUSIONS: Our results indicate that HLA-A*2601 is possibly associated with ocular BD, independent of HLAB* 5101, indicating that HLA-A*2601 is an additional susceptibility allele candidate of ocular BD in Japan. HLAA* 2601 would also be a possible marker for poor visual prognosis.