The association of HLA-DRB1 alleles with rheumatoid arthritis in the Chinese Shantou population: a follow-up studyThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.

Abstract

We investigated the distribution of HLA-DRB1 alleles in a sample of the Chinese Shantou population, and explored the relationship between HLA-DRB1 alleles and the susceptibility and clinical features of rheumatoid arthritis (RA). We studied 117 consecutive patients with RA and control groups, including 38 cases of systemic lupus erythematosus and 100 healthy individuals. HLA-DRB1 genotyping was performed using PCR with sequence-specific primers. HLA-DRB1*04 subtypes were detected using spot hybridization of PCR products with sequence-specific oligonucleotide probes. We compared the frequency of HLA-DRB1 alleles in healthy control patients with that in patients with RA. Patients with RA were evaluated for sex, age at disease onset, disease duration, extra-articular involvement, presence of autoantibodies, global functional status, and radiographic damage. The frequency of HLA-DRB1*04 was found to be significantly higher in RA patients than in healthy individuals (49.6% vs 18.0%, odds ratio = 4.478, P< 0.001). HLA-DRB1*0405 was the most prominently associated subtype in RA patients (62.1% vs 27.8%, odds ratio = 4.255, P = 0.011). Compared with the HLA-DRB1*04-negative RA group, the mean duration of RA in the HLA-DRB1*04-positive RA group was longer, and the mean age at disease onset was lower. A 2-9 year follow-up study was performed, and the risk factors associated with the radiographic progression of RA were determined. Logistic regression analysis revealed that only HLA-DRB1*04 alleles were significantly associated with the radiographic progression of RA (B = 2.652, P = 0.018, Exp(B) = 14.182). Our observations indicated that the HLA-DRB1*04 alleles, especially the subtype HLA-DRB1*0405, were significantly associated with RA susceptibility in the Chinese Shantou population. The HLA-DRB1*04 alleles may be associated with the severity of RA.

Shared Epitope Alleles Remain A Risk Factor for Anti-Citrullinated Proteins Antibody (ACPA) – Positive Rheumatoid Arthritis in Three Asian Ethnic Groups

“…but was lower in comparison with Caucasians RA patients (81.6% in Northern Irish and 87.7% in Southern Swedish) [26], [27]. On the other hand, the frequency of SE alleles in the European healthy controls was also relatively high (54.9% in Northern Irish and 50% in Southern Swedish), when compared with various healthy controls in the Asian populations [9], [10], [11], [13], [26], [27]. Notably, out of the three ethnic groups in our study, Indian RA patients and controls had a slightly higher frequency of SE (56% in Indians RA vs. 28.6% in Indian controls), though it was still lower than in European Caucasian populations [26], [27].…”

“…DRB1*0401, *0404 and *0408 are associated with RA in Caucasians, while the disease is mainly associated with DRB1*0405 in East Asians [7], [8], [9], [10], [11], [12], [13], [14]. In other ethnic groups, it has been well established that alternative HLA-DRB1 alleles might be associated with RA, either instead of or in addition to DRB1*04.…”

Extraarticular Manifestations of Rheumatoid Arthritis in a Multiethnic Cohort of Predominantly Hispanic and Asian Patients

“…Genetic differences are plausible contributors to the differential development of ExRA in Hispanic and Asian patients 39,40. These 2 ethnic groups differ in the HLADRB1 allelic variants that contribute to genetic risk of developing RA, and in the prevalence of the PTPN22 C1858T polymorphism, which confers risk for development of RA in white patients 10,11,17,19,22,25. It is unlikely, however, that these particular risk alleles contribute to the differences in ExRA in our cohort.…”

The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese

“…The genotyping for HLA-DRB1 was performed using PCR–SSP as described previously [22]. The PCR amplifications were performed at 94°C or 1 min followed by 30 cycles, and the amplification conditions were different depending on HLA-DRB1*01–DRB1*10 specificities [22].…”