Genetics of Endocrine Disorders and Diabetes Mellitus
George H. Gass, Harold M. Kaplan in Handbook of Endocrinology, 2020
The particular HLA antigens associated with susceptibility or resistance to IDDM vary somewhat from one population to another. The DR3 allele is found to be associated with IDDM susceptibility in Caucasian,5,6 Chinese,7 and Finnish8 populations. HLA-DR4 is a susceptibility allele in Caucasian,5,6 Finnish,8 and Japanese9,10 populations. DR9 is associated with susceptibility in Japanese IDDM.9,10 The DR2 allele is considered protective from IDDM in Caucasians5,6 and Japanese.9,10 The presence of aspartate at position 57 of the DQ α chain is usually associated with resistance to IDDM, and the presence of an arginine at position 52 of the DQ β chain is associated with susceptibility to IDDM in Japanese9,11 and Caucasian12,13 populations.
Non-viral liver disease
Michael JG Farthing, Anne B Ballinger in Drug Therapy for Gastrointestinal and Liver Diseases, 2019
Although the aetiological factors remain unknown, it is accepted widely that PBC arises in a susceptible individual, usually female, as a result of one or more environmental trigger factors. Evidence from family studies has shown that inherited factors play an important role in determining disease susceptibility.33, 34 Two studies have shown that the prevalence of PBC in first-degree relatives is 4–6%, significantly higher than the highest reported whole population prevalence.35 Unlike the two other autoimmune diseases, autoimmune hepatitis and primary sclerosing cholangitis, PBC is not associated with an over representation of the HLA A1 B8 DR3 DR52a haplotype, nor are there secondary associations with HLA DR4 or DR2 as reported in these conditions. Several genotyping studies from different populations have demonstrated a positive association between HLA Class II antigen DR8 and PBC;36 however, the association only accounts for a few patients with PBC. This may reflect the fact that the susceptibility allele lies some distance from the HLA DR genes.
Inflammatory rheumatic disorders
Ashley W. Blom, David Warwick, Michael R. Whitehouse in Apley and Solomon’s System of Orthopaedics and Trauma, 2017
Genetic susceptibility A genetic association is suggested by the fact that RA is more common in first-degree relatives of patients than in the population at large; furthermore, twin studies have revealed a concordance rate of around 30% if one of the pair is affected. The human leucocyte antigen (HLA) DR4 occurs in about 70% of people with RA, compared to a frequency of less than 30% in normal controls. HLA-DR4 is encoded in the major histocompatibility complex (MHC) region on chromosome 6. There are strong associations between HLA-DR4 and RA. In particular, a key structural conformation within the HLA-DR4 binding groove called the ‘shared epitope’ seems important. This may suggest that a particular antigen that fits into this may be playing a part.
Comparative study of HO-1 expressing synovial lining cells between RA and OA
Published in Modern Rheumatology, 2021
Suran Yang, Rintaro Ohe, Naing Ye Aung, Tomoya Kato, Takanobu Kabasawa, Aya Utsunomiya, Yuya Takakubo, Michiaki Takagi, Mitsunori Yamakawa
Recent researches have proposed a novel mechanism regarding the onset of autoimmune diseases [13,14]. Under inflammatory conditions accompanied with secretion of inflammatory cytokines, MHC class II is expressed on non-immunocompetent cells normally lacking of MHC class II, and, further, the complex of denatured protein as antigen and MHC class II is accidentally presented on cells with binding to an invariant chain and capping. Consequently, denatured protein is recognized by autoreactive B cells as ‘neo-self’, leading to the production of autoantibodies. In RA, human leukocyte antigen (HLA)-DR4 is widely known as a representative MHC class II. The presentation of a complex of denatured protein, IgG-Fc, and HLA-DR on the cell membrane leads to the production of an antibody, rheumatoid factor (RF) [13,14]. It is, however, a mystery what kind of cells present denatured IgG-Fc in human RA. No studies have focused on the relationship between antibody-producing cells and the HO-1 expressing cells.
miR-148b-3p affects the pathogenesis of adjuvant-induced arthritis rats through the direct target DNMT1
Published in Autoimmunity, 2018
Chenggui Miao, Hao Yu, Jun Chang, Guoxue Zhang, Guoliang Zhou, Chuanlei Zhao
RA is a chronic systemic autoimmune disease consisting mainly of joint disease. The main clinical manifestations are joint swelling and pain caused by FLS abnormal proliferation, followed by the cartilage damage, joint space narrowing, severe bone destruction, eventually leading to the joint stiffness, deformity, dysfunction [22]. Clinical observations suggest that RA can develop at any age, and the age of the highest incidence is 40–50 years old. The disease is mostly a recurrent disease, the morbidity is higher, the prognosis is poor, and there is no cure for RA patients [23]. The cause of the disease is not yet clear. However, studies have shown that RA is a disease that is closely related to environmental, bacterial, viral, genetic, sex hormones and neuropsychiatric status [24]. For example, the RA incidence rate is higher in some families, and the genetic factor may be one of the causes of this disease. In a population survey, it was found that human leukocyte antigen (HLA)-DR4 was associated with RF-positive patients. HLA study also found that DW4 was associated with the incidence of RA. Data showed that 70% of patients is HLA-DW4 positive, these patient has the site of the susceptible gene, so the genetic factor may play an important role in the pathogenesis of RA [25].
Human-leukocyte antigen class II genes in early-onset obsessive-compulsive disorder
Published in The World Journal of Biological Psychiatry, 2019
Natalia Rodriguez, Astrid Morer, E. Azucena González-Navarro, Patricia Gassó, Daniel Boloc, Carles Serra-Pagès, Amalia Lafuente, Luisa Lazaro, Sergi Mas
Strong, confirmed associations of HLA-DR4 with the risk of autoimmune diseases such as RA and T1D have been reported by numerous studies (Miyadera & Tokunaga 2015). In Caucasian populations, alleles HLA-DRB1*04:01 and 04:04 are responsible for the stronger associations reported for RA. These alleles carry a shared epitope at amino acid positions 70β to 74β, which may be responsible for the mechanism of action underlying the association between HLA-DRB1 and autoimmune diseases (Raychaudhuri et al. 2012). Two models have been proposed to explain these associations (Miyadera & Tokunaga 2015). In the peptide-specific model, the associations of HLA with autoimmune diseases may be explained by the selective presentation of disease-relevant self-peptides by the disease-susceptible HLA allele products. In contrast, the HLA stability model proposes that intrinsically unstable HLA proteins (susceptibility alleles), which form unstable HLA-peptide complexes through the presentation of diverse self-peptides, increase the risk of autoimmune diseases.
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