The MHC region, encoding the HLA glycoproteins, consists of a complex of genes located on chromosome 6p21 (Figure 1). The MHC region also encodes various additional proteins, most of which are associated with immune responsiveness. Since this gene region is highly polymorphic and contains many immune response genes it was the first candidate genetic region to be studied for association and linkage with AITD.

Fig1. The HLA region is located on chromosome 6p21. It is a complex genetic region which consists of several loci, all of which code for proteins which influence the different arms of the immune system. Depicted are the major loci.

Association of HLA with GD: GD was initially found to be as sociated with HLA- B8 in Caucasians. This finding was then con firmed in a wide number of studies, mostly examining populations of Caucasian origin (Table 31). In these early studies HLA- B8 was associated with relative risks for GD ranging from 1.5 to 3.5. Subsequently, it was found that GD was more strongly associated with HLA- DR3, which is in LD with HLA- B8. The frequency of DR3 in GD patients was 40– 55% and in the general population 20– 30% giving a relative risk for people with HLA- DR3 of 2– 3. Even though the frequency of HLA- DR3 was increased in Caucasians with GD, there were also HLA- DR3 negative associations with GD, and in addition, the HLA associations were found to be different in other ethnic groups (Table 2). In the Japanese population GD was associated with HLA- B35, and in the Chinese population an increased frequency of HLA- Bw46 was reported. In African Americans, no overall susceptibility could be associated with any DR allele, although subdivision of the patients revealed that DRw6 was associated with thyroid antibody formation. Among Caucasians, HLA- DQA1*0501 has also been associated with Graves’ disease (Table 1), but it appears that the most common susceptibility allele in GD is indeed HLA- DR3 (HLA- DRB1*03).

Table1. Some of the important HLA association studies in Graves’ disease performed in Caucasians

Table2. Some of the important HLA association studies in Graves’ disease performed in non- Caucasian populations

The exact amino- acid sequence in the DRβ1 chain conferring susceptibility to GD was determined by sequencing the HLA- DRB1 locus in a population of GD patients and controls. These studies identified arginine at position 74 of the HLA- DRβ1 chain (DRβ- Arg74) as the most critical DR amino acid conferring susceptibility to GD [25]. Further analysis showed that the presence of glutamine at position 74 was protective for GD. This suggests that position 74 of the DRβ1 chain is critical for GD development in certain patients but not in others. Recent work suggests that certain TSHR and Tg peptides, in particular, have higher affinity for these HLA- DR pocket sequences.

Not only has the association with ‘disease’ been explored but the role of HLA polymorphisms may be critical for the clinical expression of the different GD phenotypes. Some groups reported an as sociation between the likelihood of relapse of GD with HLA- DR3 while others were unable to confirm this. Studies of HLA associations in GO have also produced conflicting results with some workers reporting increased frequency of HLA- DR3 in patients with GO, and others reporting no difference in the distribution of HLA- DR alleles between GD patients with and without ophthalmopathy. Likewise, no difference in the DR3 frequency was found in GD patients with and without pretibial myxoedema. It appears, therefore, that HLA provides a broad degree of susceptibility rather than for any particular phenotype.

Association of HLA with Hashimoto’s thyroiditis: Data on HLA haplotypes in HT have been much less definitive than in GD (see Table 3). Early studies suggested an association of goitrous HT with HLA- DR5 (RR = 3.1) and of atrophic HT with DR3 (RR = 5.1) in Caucasians. Later studies in Caucasians reported weak associations of HT with HLA- DR3 and HLA- DR4. Associations of HT with other HLA haplotypes have also been reported in different ethnic populations (e.g. HLA- DRw53 in Japanese, and HLA- DR9 in Chinese). An HLA- DR pocket amino acid signature was found to confer a strong risk for HT resulting in an odds ratio of 3.7 [26] from a unique pocket structure that could influence the binding of pathogenic peptides to the HLA- DR pocket and their presentation to T cells. In addition, studies suggest that certain Tg peptides, in particular, have affinity for these specific HLA- DR pocket sequences.

Table3. Some of the important HLA association studies in Hashimoto’s thyroiditis

اخر الاخبار

اخبار العتبة العباسية المقدسة

قسم الشؤون الخدمية يواصل جهوده في توزيع الماء لزائري مرقد أبي الفضل العباس (عليه السلام)

قسم شؤون المعارف يجري القرعة الإلكترونية الخاصة بمشاهدي (مسابقة معارف التراث)

قسم الشؤون الفكرية يواصل برنامجه الصحي التوعوي في مدارس بغداد

من خدمة الزائرين إلى إغاثة المنكوبين.. العتبة العباسية المقدسة حاضرة في كل الميادين

المزيد

الآخبار الصحية

كوب قبل النوم.. مشروب طبيعي يحارب الأرق

دون أدوية.. طريقة طبيعية لخفض ضغط الدم بفعالية مذهلة

المعكرونة ليست عدوك.. كيف تصبح جزءا من وجبة صحية متوازنة؟

دراسة: تناول القهوة يوميا يخفض خطر الإصابة بالاضطرابات النفسية

المزيد

الآخبار التكنلوجية

علماء روس يخططون لبناء منشأة للكشف عن المادة المظلمة

ثاني أكسيد الكربون ليس تهديدا للمناخ فقط.. بل لصحة الإنسان أيضا!

ديدان الأرض تكشف تلوث التربة بالمعادن الثقيلة

خبير أرصاد جوية: ظاهرة النينيو القادمة قد تكون الأقوى خلال 10 سنوات

المزيد

مواضيع ذات صلة

The Complex Genetics of Thyroid Disease : Mechanisms of Disease Induction by Susceptibility Genes

Genetics of Autoimmune Thyroid Disease : Non- HLA Genes in AITD

Genetic Susceptibility to Autoimmune Thyroid Disease (AITD)

Maternal Inheritance of Disorders Caused by Variants in the Mitochondrial Genome

Genetic Screening in Populations

Genetic Counseling for Preconception and Prenatal Diagnosis and Screening

Fetal Surgical and Medical Interventions

X-Linked Inheritance

Preconception Genetic Screening and Testing

Problems in Prenatal Chromosome Analysis and Gene Sequencing

Introduction to Cytogenetics and Genome Analysis

Methods to Detect Fetal Chromosomal Abnormalities