Association between HLA-B*46 Allele and Graves Disease in Asian Populations: A Meta-Analysis

Abstract

Graves' disease (GD) is a leading cause of hyperthyroidism, which affects 1.0-1.6% of the general population. Previous studies reported a higher GD prevalence in Asian populations compared to Caucasian populations. The etiology of GD involves complex interactions between predisposing genes and environmental triggers. Genetic studies have shown that the human leukocyte antigen (HLA) is an important candidate genetic region associated with GD in Asian populations. However, the results were inconsistent and inconclusive. Here, we performed a meta-analysis to evaluate the role of the HLA-B*46 allele in GD in Asian populations. A total of 14 case-controlled studies on the association of the HLA-B*46 allele in 1743 GD patients and 5689 controls were included. Our results showed a trend toward an increased risk of GD in HLA-B*46-positive subjects compared to those HLA-B*46-negative (OR = 2.48; 95% CI = 1.96-3.13, P < 0.01). However, there were some limitations to the current meta-analysis, such as heterogeneity (Pheterogeneity < 0.01 and I2 = 68.0%) or the different typing methods (serological and genotyping methods). The meta-analysis indicated that the HLA-B*46 allele is a risk factor for GD in Asian populations. Future studies on the role of the HLA-B*46 allele in GD should consider complications such as periodic paralysis, ophthalmopathy and recurrence.

Systemic sclerosis patients are at higher risk of hyperthyroidism and have a worse survival than those without hyperthyroidism: A nationwide population‐based cohort study

“…HLA‐DR3 association was also reported in Graves' disease, the most common autoimmune aetiology of hyperthyroidism. Associations of HLA‐DRB1 with both diseases were also reported . Secondly, in autoimmune conditions, there might be a nonspecific production of autoantibodies unrelated to the primary autoimmune condition.…”

Association between TSHR gene polymorphism and the risk of Graves' disease: a meta-analysis

“…It affects up to approximately 1% of the general population [1] , and the studies in twins suggest that genetic factors contribute 80% to the etiology of GD [2] . Previous works have identified several gene loci that are associated with the risk to develop GD, which include human leukocyte antigen (HLA) [3-4] , cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) [5] , thyroid stimulating hormone receptor (TSHR) [6-9] , thyroglobulin (TG) [10-11] , protein tyrosine phosphatase ( PTPN ) gene [12-13] , CD40 gene [14-16] , Fc receptor-like protein 3 ( FCRL3 ) gene [16] , vitamin D receptor ( VDR ) gene [17] , and interleukin-1 gene [18] . In recent years, a number of new genes have been reported which may be associated with the etiology of GD, including the methylenetetrahydrofolate reductase ( MTHFR ) gene [19] , CD24 gene [20] , mannose-binding lectin2 ( MBL2 ) gene [21] , NACHT leucinerich repeat protein 1 ( NLRP1 ) gene [22] , and signal transducer and activator of transcription 3 ( STAT3 ) gene [23] .…”

PharmGKB summary

“…These include HLA-B*53 and resistance to malaria [9, 10], HLA-B*51 and susceptibility to the inflammatory condition Beçhet's disease [11, 12], and HLA-B*46 and increased risk of Graves’ disease, an autoimmune disorder [13]. Two particularly strong disease associations are HLA-B*57 and HIV long-term non-progression, and HLA-B*27 and ankylosing spondylitis.…”