Relationship between obstructive sleep apnea and human leukocyte antigen variants

Background and aim: The obstructive sleep apnea (OSA) is a common, complex and polygenic disease and it has high risk of serious complications. The human leukocyte antigen (HLA) system plays a crucial role in the regulation of immune function by discriminating self from non-self. In recent years there has been rapid advancement in "Next Generation Sequencing" technology. It enables the detection of HLA alleles in four or even six digits, providing a high level of precision. The aim of the present study was to investigate the genetic variants at HLA-A,-B,-C,-DQB1 and -DRB1 loci in OSA patients and unrelated healthy individuals by targeted NGS in the Turkish population. Materials methods: Fifty newly diagnosed patients with OSA and 50 control subjects were enrolled in the study. OSA diagnosis was made by utilizing the apnea-hypopnea index (AHI)≥5 in overnight polysomnography (PSG). Blood samples were obtained in the morning, after PSG. Controls were randomly selected from healthy volunteers who had a low risk for OSA. Genotyping of HLA-A, B, C, DRB1 and DQB1 genes were performed by using next generation sequencing. Results: HLA-A*02:01, HLA-C*03:03:01, HLA-C*14:03, HLA DRB1*04:05 alleles were found more frequently in OSA patients, but not in the controls (p=0.036, p=0.007, p=0.043 and 0.013, respectively). The allele frequencies of HLA-A*03:01 and HLA-B*35:02 were significantly higher in controls compared to OSA patients (p=0.024 and p=0.043). Conclusion: These results suggest that HLA-A*02:01, HLA-C*03:03:01, HLA-C*14:03, HLA DRB1*04:05 alleles may play a predisposing role in the Turkish population with OSA. In addition, HLA-A*03:01 and HLA-B*35:02 alleles may be protective in this population.

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Distribution of HLA epitope frequencies in Turkish population

Turkish Journal of Biochemistry ◽

10.1515/tjb-2021-0083 ◽

2022 ◽

Vol 0 (0) ◽

Author(s):

Fatma Savran Oguz ◽

Suleyman Rustu Oguz ◽

Yeliz Ogret ◽

Tanju Sedat Karadeniz ◽

Hayriye Senturk Ciftci ◽

...

Keyword(s):

Next Generation Sequencing ◽

Human Leukocyte Antigen ◽

Healthy Volunteers ◽

Hla Antigens ◽

Human Leukocyte ◽

Turkish Population ◽

Next Generation ◽

Leukocyte Antigen ◽

Shared Epitopes ◽

Generation Sequencing

Abstract Objectives The antibodies interact with the “Human Leukocyte Antigen (HLA) antigens” at specific epitopes. “Epitopes” are present on a single HLA or shared by multiple antigens. In this study, we aim to determine the frequency of prevalent epitopes common in the Turkish population. Methods Non-related 644 healthy volunteers were recruited, and The “HLA-A, -B, -C, -DR -DQ’s” were typed using the “Next Generation Sequencing”. The provisional and confirmed epitopes were identified using the “HLA Epitope Registry databases, HLA Epitopia Maps and Immucor Epitope databases” dated 07.02.2018. Epitope frequencies were calculated by counting the shared epitopes in the total number of shared HLA Class epitopes in our sample database. Results Class I HLA’s had 298 epitopes that repeated a total of 158,117 times with frequencies ranging between 0.0006 and 2.03%, and the most frequent epitope was 170RY found on 119 different alleles. Class II HLA’s had 193 epitopes that repeated a total of 93,082 times with frequencies ranging between 0.002 and 1.36%, and the most frequent epitope was 108P found on 42 different alleles. Conclusions Our findings summarize both the provisional, and confirmed epitope frequencies in the Turkish population and may help clinicians and immunogeneticists develop a better understanding of HLA epitope mismatches.

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