Yi Lin

Human leukocyte antigen DPB1 was reported to contain singly nucleotide polymorphisms conferring the strongest susceptibility to systemic sclerosis in Korean population. However, associations of specific DPB1 alleles with SSc vary in different ethnic populations. The aim of this study was to profile DPB1 alleles in Chinese population and to identify specific DPB1 alleles in association with SSc and clinical and serological features of SSc in Han Chinese. A cohort containing 338 patients with SSc and 480 gender-matched and unrelated controls were examined in the study. The HLA-DPB1 genotyping was performed with sequence-based typing method. Exact p-values were obtained (Fisher's test) from 2×2 tables of allele counts or allele carriers and disease status. Thirty eight DPB1 alleles were found in the cohort. DPB1*05:01 was the most common allele in this cohort. DPB1*03:01 and *13:01 were significantly increased in SSc. DPB1*13:01 association had already been described in other ethnic populations, whereas DPB1*03:01 was specific to Han Chinese patients with SSc. In addition, comparisons between SSc subsets indicated that patients carrying DPB1*03:01 were more likely to develop pulmonary fibrosis, DPB1*04 carriers were increased in SSc patients with anti-centromere autoantibodies and in contrast, SSc patients with homozygous DPB1*05:01 showed an opposite association with marginal significance.

Specific human leukocyte antigen (HLA) DQB1 alleles confer strong susceptibility to systemic sclerosis (SSc). However, the frequencies of specific DQB1 alleles and their associations with SSc vary according to ethnicity and clinical features of SSc. The aim of this study was to profile DQB1 alleles in a Chinese population and to identify specific DQB1 alleles in association with SSc of Han Chinese. A cohort containing 213 patients with SSc and 239 gender-matched and unrelated controls was examined in the study. The HLA-DQB1 genotyping was performed with sequence-based typing (SBT) method. Exact p-values were obtained (Fisher's test) from 2x2 tables of allele counts or allele carriers and disease status. Seventeen DQB1 alleles were found in the cohort. DQB1*03:03 was the most common allele in this cohort. DQB1*05:01 was significantly increased in SSc, and was strongly associated with anti-centromere autoantibodies (ACA). Compared with SSc in other ethnic populations, SSc patients of Han Chinese are distinct in association with DQB1*06:11, common in association with DQB1*05:01, but lack association with DQB1*03:01. In addition, DQB1*06:01 appeared more common in ATA-positive Chinese SSc, and marginally associated with pulmonary fibrosis, and an increased frequency of DQB1*03:03 was observed in anti-U1RNP-positive Chinese SSc patients.

Systemic sclerosis (SSc) is a complex disease involving multiple genetic factors. An association of the IRF5 polymorphism with SSc was reported in Caucasian populations of Europe and North America, as well as in Japanese populations. The present study aimed to examine whether the SSc-associated SNP rs2004640 of IRF5 gene confer susceptibility to SSc and clinical features of SSc in a Han Chinese population. A Han Chinese cohort consisting of 424 SSc patients and 502 healthy controls were examined in the study. TaqMan assays were carried out to examine the SNP. Exact p-values were obtained (Fisher’s test) from 2x2 tables of allele counts and disease status. SSc patients of Han Chinese showed increased homozygous TT genotype of the rs2004640 (p = 0.027, odds ratio (OR) = 1.4, CI =1.03-1.93), which was significantly associated with pulmonary fibrosis of SSc and ATA-positive SSc of Han Chinese. The lcSSc and ACA-positive SSc of Han Chinese appeared also in association with the increased T allele frequency. However, the Chinese dcSSc did not show any association with the rs2004640. The results were consistent with previous reports in other ethnic populations in supporting the notion that polymorphisms of IRF5 may play an important role in susceptibility to SSc.

Human leucocyte antigen (HLA) B*27 is a susceptibility allele to ankylosing spondylitis (AS). However, major AS-associated subtypes of HLA-B*27 and other HLA-B alleles vary in different ethnic populations. Herein, we examined HLA-B alleles in a total of 360 AS patients and 350 controls of Chinese Han ancestry. The HLA-B genotyping was performed with sequence-based typing (SBT) method. Six HLA-B*27 subtypes B*27:04, B*27:05, B*27:07, B*27:08, B*27:10 and B*27:15 were observed in the cohorts. HLA-B*27:04:01 and -B*27:05:02 appeared significantly increased in AS patients, which indicated as two major susceptibility alleles to AS. Homozygous B*27 was observed only in AS patients. There are 30 HLA-B alleles identified in the studies. HLA-B*15, especially B*15:01:01:01, appeared as the major allele type in the Chinese controls. Some common HLA-B alleles such as HLA-B*15, B*13, B*46 and B*51 were significantly reduced in Chinese AS patients. In conclusion, the studies profiled the HLA-B alleles, and identified major susceptibility subtypes of B27 to AS in Han Chinese population