Major Histocompatibility Complex, Class I, C

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OMIM Number

142840

NCBI Gene ID

3107

Uniprot ID

P10321

Length

3,388 bases

No. of Exons

8

No. of isoforms

2

Protein Name

HLA class I histocompatibility antigen, C alpha chain

Molecular Mass

40649 Da

Amino Acid Count

366

Genomic Location

chr6:31,268,749-31,272,136

Gene Map Locus
6p21.33

Description

The genes of the Human Leukocyte Antigen (HLA) system are located on chromosome 6, and code for cell-surface proteins that play a crucial role in the presentation of endogenic peptides to effector cells of the immune system. The HLA Class I protein molecule is a heterodimer, made up of two chains; a heavy one, and a light one (beta 2 microglobulin). The HLA-C gene is one of the three HLA Class I heavy chain paralogues.

Just like the HLA Class I A and B types of molecules, HLA-C is also involved in the presentation of foreign antigens to the immune system. However, HLA-C has also been shown to function as a ligand of killer cell immunoglobulin-like receptor (KIR) molecules. In addition, recent studies have proved that HLA-C protein molecules act as inhibitors of the lytic capacity of natural killer (NK) cells and non-MHC-restricted T-cells. Diseases known to be associated with the HLA-C locus include multinodular goiters (Cw1) and B cell chronic lymphocytic leukemia (Cw*16).

Epidemiology in the Arab World

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Other Reports

Jordan

Sánchez-Velasco et al. (2001) studied major histocompatibility complex (MHC) class I and class II alleles in 100 unrelated adult Jordanians of both sexes from the capital Amman and in 46 individuals from the Jordan valley. HLA-C*0502 (0.1793), C*0401 (0.1000), and C*0602 (0.0827) were found to be the three most frequent alleles among Jordanians.

Kuwait

Zaki et al. (1994) carried out a case control study involving a group of 48 Arab children with steroid responsive childhood nephritic syndrome and a control group consisting of healthy Arab children, to see if there was any HLA association in this population. HLA-CW6 was found to be significantly increased, while HAL-CW4 was significantly decreased in the patient group.

Mahmoud (1998) studied the expression frequencies of the major histocompatibilty complex (MHC) in 26 Kuwaiti patients with psoriasis and 60 controls matched for age, sex, and ethnic origin. The study revealed significantly increased expression of HLA-CW6 in the cases versus the controls.

Lebanon

Allele frequencies of HLA -C alleles were studied in the Lebanese population by Cano et al (2012) and Buhler et al (2006).  

Khansa et al. (2013) conducted a study to investigate the distribution of HLA-A, -B and -C alleles in Lebanon. HLA typing for class I A, B, and C alleles were carried out in a group of 1994, 1309, and 1163 potential donors (bone marrow/kidney), respectively. The study identified A*02:01, B*35:01, and C*04:01 as the most common class I alleles among these unrelated subjects, from different parts of Lebanon.

Oman

Agarwal et al. (1996) compared the frequencies of HLA-C antigens in 50 Omani patients diagnosed with Idiopathic Dilated Cardiomyopathy, with those of 247 healthy Omani control subjects. Data obtained were statistically analyzed by chi square test or the Fisher exact test (where appropriate) with the Bonferroni correction obtained by multiplying the P value by the numbers of antigens tested to correct the P value for any chance associations (PC). The antigens tested for included HLC w1, w2, w3, w4, w5, and w6. None of these antigens showed a significant difference in frequency between the patient and control group. The most common antigens in both groups were HLA-Cw4 (32% in patient, and 34% in control group), HLA-Cw3 (28% in patient, and 14% in control group), and HLA-Cw6 (14% in patient, and 14% in control group).

Saudi Arabia

Abanmi et al. (2005) investigated the association between HLA-C (Alanine-73 and Aspartate-9) and susceptibility to psoriasis among Saudi patients.  Using specific primers to detect nucleotide coding sequence for Ala-73 and Asp- 9 were applied for 25 PsV patients and 75 controls.  The frequency of Asp-9 was significantly higher in PsV patients as compared to controls accounting for 84% and 61%, respectively.  There was no significant difference in Ala-73 frequencies among PsV patients and controls.  Patients and controls that were positive for Asp-9 were also positive for Ala-73, except one control.  One year later, Abanmi et al. (2006) investigated the HLA loci antigens and alleles in a group of 40 unrelated Saudi patients with vitiligo (18 males, 22 females) and compared the results to that in a group of 40 matched controls.  The most frequent HLA-C antigens among the patient group were Cw4, Cw6, and Cw7.  The statistically significant difference between HLA-C antigens among the disease and control groups were the frequencies of HLA-Cw6 and Cw7, both of which were found to be increased in vitiligo patients.

United Arab Emirates

Al Yafei et al. (2019) described a novel HLA-C allele identified in an Emirati subject. The new allele was named HLA-C*16:123N and differed from C*01:02:01:01 by a single substitution.

Al-Yafei et al. 2020 studied the distribution of HLA alleles in 77 unrelated Emiratis. The common HLA-C alleles identified among these subjects were C*06:02:01 (18%), C*04:01:01 (14%), and C*07:02:01 (12%).

Kulski et al. 2019a studied HLA class I alleles in 95 unrelated and healthy Bedouins from the UAE. The most frequent HLA-C allele lineages identified were C*07 (0.216), C*06 (0.163) and C*04 (0.153). The common three-loci haplotypes were HLA‐A*02 ~ HLA‐C*06 ~ HLA‐B*50 (0.068), HLA‐A*02 ~ HLA‐C*07 ~ HLA‐B*08 (0.044), and HLA‐A*11 ~ HLA‐C*15 ~ HLA‐B*40 (0.042). Comparison of HLA allele lineage frequencies in the UAE Bedouins with different world populations indicated genetic similarity with Saudi Arabians from the west and Omanis from the south of the Gulf Peninsula.

Kulski et al. 2019b reported on five polymorphic Alu insertions (POALINs) within class I region of the MHC in 95 unrelated Arabs from the UAE. The five POALINs examined in the study were AluHF, AluHG, AluHJ, AluTF and AluMICB, of which AluHG*02 (AluHG insertion) had the highest frequency (0.332). Comparison of five MHC POALIN frequencies in the UAE Arabs with 30 different world populations using multidimensional scaling revealed clustering that was relatively closer to distinct groups of Australian Caucasians, Spanish, British and British Indians. Phylogenetic analysis showed distribution of the UAE Arabs closer to distinct clusters comprising the Spanish subpopulations and the Indians from East Midland of the United Kingdom.

Arnaiz-Villena et al. 2019 characterized HLA alleles in 52 blood donor volunteers from Abu Dhabi, UAE. HLA typing was carried out for HLA-A, HLA-B, HLA -C, HLA-DRB1, HLA-DQB1, and HLA-DQA1 alleles. Twenty-two HLA-C alleles were identified in these subjects.

Creary et al. 2021 characterized HLA alleles and diversity across populations worldwide. One population involved 52 Emirati individuals (104 chromosomes). HLA-A, HLA-C, HLA-B, HLA-DRB1, HLA-DRB3/4/5, HLA-DQA1, HLA-DQB1, HLA-DPA1, HLA-DPB1 alleles were typed in this population. 26 unique HLA-C alleles were identified in the Arab population. 

Tay et al. 2021 identified three HLA-DR4 haplotypes in seven children with type I diabetes from five Emirati families: HLA-DRB1∗04:01:01-DQB1∗03:02:01:01; HLA- DRB1∗04:02:01-DQB1∗03:02:01; and HLA-DRB1∗04:05:01-DQB1∗02:02:01:02. These haplotypes were previously associated with Type 1 Diabetes in Arabs. The study study additionally reported on HLA-DR4 and HLA-DR3 T1D risk haplotypes in the parents. Haplotypes HLA -A*26-B*08-DRB1*03 and HLA -C∗06-B∗50-DRB1∗03:01-DQ∗02 were also identified, previously associated with diabetes in North Indians. 

Alnaqbi et al. 2021 investigated the contribution of 20 HLA antigens to COVID19 severity in 115 Emirati patients. The study analyzed 20 HLA alleles involving HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1.HLA-B*51:01 and  HLA-A*26:01 was negatively associated with severity, whereas HLA-A*03:01, HLA-DRB1*15:01, and supertype B44 was positively associated with severity.

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