The association of HLA-DQB1*0602 but not HLA-DRB1*15 with obstructive sleep apnea

Momany, Suleiman; Al-Qatarneh, Thamer; Khader, Yousef; Abuharfeil, Nizar Mohammad; Daoud, Ammar K.; Mahasneh, Amjad

doi:10.25011/cim.v40i4.28494

Cited by 3 publications

(6 citation statements)

References 47 publications

(61 reference statements)

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“…No allele related association was detected for the HLA-DQB region. However, Manzotte and Momany has previously reported in their study that there was a relationship between the HLA-DRB1 * 0602 allele and the incidence of OSA (23,24). They considered this allele as a predisposing allele.…”

Section: Discussionmentioning

confidence: 91%

Relationship between obstructive sleep apnea and human leukocyte antigen variants

Zamani

Yosunkaya

Zamanı

et al. 2021

Preprint

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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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Section: Discussionmentioning

confidence: 91%

Relationship between obstructive sleep apnea and human leukocyte antigen variants

Zamani

Yosunkaya

Zamanı

et al. 2021

Preprint

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“…Some of these haplotypes might have a role in disease development and progression through the interaction with HLA-DQB1*0602. Since HLA-DQB1*0602 was found to associated with OSA [19,20] , and the attack of HLA-DQB1*0602 and HLA-DQA1*0102 on hypocretin-secreting neurons in narcolepsy [30] ; this suggesting that the five variations that change the amino acids might interaction with HLA-DQB1*0602 and HLA-DQA1*0102 to attack on hypocretin-secreting neurons. Still this needs to be more investigated because there could be other variants in different genes including HLA genes combine with the 8 variants in this study by the mechanism of linkage disequilibrium and form more specific haplotypes that might interfere with OSA development, or work as markers for OSA.…”

Section: Discussionmentioning

confidence: 99%

“…Peripheral blood samples from both OSA patients and controls were collected into 3ml-EDTA tubes (a total of 80 samples, a 3 ml each). Genomic DNA was isolated from venous blood lymphocytes by using a commercially available kit (Puregene Blood Kit; Qiagen, Germany), the polymerase chain reaction was carried out using 2x PCR Master mix Solution (i-MAX TM II) kit, and for Gel Electrophoresis: 5 µl of each PCR product was loaded into wells of 2.3% agarose gel (Bio Basic, Canada) [20] . All positive samples from PCR that contain the amplified fragment of (HLA-DQB1*0602 allele) from 40 patients and 40 control samples [20] ; were purified and amplified again using forward or reverse primers which were used in the PCR.…”

Section: Materials and Methods Ethical Clearancementioning

confidence: 99%

“…Genomic DNA was isolated from venous blood lymphocytes by using a commercially available kit (Puregene Blood Kit; Qiagen, Germany), the polymerase chain reaction was carried out using 2x PCR Master mix Solution (i-MAX TM II) kit, and for Gel Electrophoresis: 5 µl of each PCR product was loaded into wells of 2.3% agarose gel (Bio Basic, Canada) [20] . All positive samples from PCR that contain the amplified fragment of (HLA-DQB1*0602 allele) from 40 patients and 40 control samples [20] ; were purified and amplified again using forward or reverse primers which were used in the PCR. DNA fragments were sequenced using 3130/3130xl Genetic Analyzer, and the reference sequence of the region in which HLA-DQB1*0602 allele is located (Ensemble ID: ENSG00000179344) was obtained from ensemble genome browser (http:// www.ensembl.org/index.html), and aligned with the sequencing electropherograms.…”

Section: Materials and Methods Ethical Clearancementioning

confidence: 99%

“…There is strong evidence suggesting that a specific HLA allele is related to a sleep disorder called Narcolepsy that shared with OSA the major symptoms of excessive day time sleepiness, this HLA allele is [13][14][15][16][17][18] . The HLA-DQB1*0602 allele was also found to be associated with OSA 19,20 . Other HLA alleles were also found to be associated with OSA such as HLA-A11 and HLA-DRB1*09 alleles 21 , and HLA-A2 22 .…”

Section: Introductionmentioning

confidence: 93%

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Human Leukocyte Antigen Genetic Variations in Obstructive Sleep Apnea Patients that were positive for HLA-DQB1*0602.

Al-Qatarneh

Momany

Abuharfil

et al. 2019

Bangladesh J Med Sci

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Background: Genetic variations in the HLA system may cause susceptibility to a large number of autoimmune and infectious diseases, and the complexity of HLA makes it hard to investigate HLA types associated with diseases. The association between HLA and Obstructive Sleep Apnea (OSA) is not well investigated due to the complexity of OSA pathogenesis; including genetic and non-genetic in different populations. Our previous study using PCR-SSPs technique showed that HLA-DQB1*0602 allele is associated with almost 6 times increase in risk in North Jordan OSA patients. Aim: The aim of this study was to see if there are any HLA genetic variations using DNA sequencing technique in the region in which HLA-DQB1*0602 is located that might interact with HLA-DQB1*0602 and affect OSA development in OSA patients who were positive for HLA-DQB1*0602 allele. Result: The DNA sequencing results showed 8 nucleotide substitution variations, which are p.G77E (c.230G>A), p.R80R (c.240C>G), p.Q85L (c.254A>T), p.R87P (c.260G>C), p.Y69D (c.205T>G), p.A70V (c.209C>T), p.A70A (c.210G>A), p.Y79Y (c.237C>T). Although only 5 variants resulted in amino acid change, all 8 variants were included in the statistical analysis, and none of these genetic variants was significant (p-value> 0.05). Additionally, eight haplotypes were detected. Some of these haplotypes might have a role in disease development through the interaction with HLA-DQB1*0602 and other genetic variants or could be as markers for OSA by the mechanism of linkage disequilibrium. Conclusion: Further studies are needed to explain the pathogenesis of OSA in terms of possible self or non-self-antigens involved. Bangladesh Journal of Medical Science Vol.18(3) 2019 p.473-478

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Comprehensive Analysis of N6-Methyladenosine Regulators in the Subcluster Classification and Drug Candidates Prediction of Severe Obstructive Sleep Apnea

Gao

Shen

et al. 2022

Front. Genet.

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Background: Obstructive sleep apnea (OSA) is the most common type of sleep apnea that impacts the development or progression of many other disorders. Abnormal expression of N6-methyladenosine (m6A) RNA modification regulators have been found relating to a variety of human diseases. However, it is not yet known if m6A regulators are involved in the occurrence and development of OSA. Herein, we aim to explore the impact of m6A modification in severe OSA.Methods: We detected the differentially expressed m6A regulators in severe OSA microarray dataset GSE135917. The least absolute shrinkage and selection operator (LASSO) and support vector machines (SVM) were used to identify the severe OSA-related m6A regulators. Receiver operating characteristic (ROC) curves were performed to screen and verify the diagnostic markers. Consensus clustering algorithm was used to identify m6A patterns. And then, we explored the character of immune microenvironment, molecular functionals, protein-protein interaction networks and miRNA-TF coregulatory networks for each subcluster. Finally, the Connectivity Map (CMap) tools were used to tailor customized treatment strategies for different severe OSA subclusters. An independent dataset GSE38792 was used for validation.Results: We found that HNRNPA2B1, KIAA1429, ALKBH5, YTHDF2, FMR1, IGF2BP1 and IGF2BP3 were dysregulated in severe OSA patients. Among them, IGF2BP3 has a high diagnostic value in both independent datasets. Furthermore, severe OSA patients can be accurately classified into three m6A patterns (subcluster1, subcluster2, subcluster3). The immune response in subcluster3 was more active because it has high M0 Macrophages and M2 Macrophages infiltration and up-regulated human leukocyte antigens (HLAs) expression. Functional analysis showed that representative genes for each subcluster in severe OSA were assigned to histone methyltransferase, ATP synthesis coupled electron transport, virus replication, RNA catabolic, multiple neurodegeneration diseases pathway, et al. Moreover, our finding demonstrated cyclooxygenase inhibitors, several of adrenergic receptor antagonists and histamine receptor antagonists might have a therapeutic effect on severe OSA.Conclusion: Our study presents an overview of the expression pattern and crucial role of m6A regulators in severe OSA, which may provide critical insights for future research and help guide appropriate prevention and treatment options.

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The association of HLA-DQB10602 but not HLA-DRB115 with obstructive sleep apnea

Abstract: The presence of HLA-DQB10602 allele, but not HLA-DRB115 allele, was significantly associated with OSA.

Cited by 3 publications

References 47 publications

Relationship between obstructive sleep apnea and human leukocyte antigen variants

Relationship between obstructive sleep apnea and human leukocyte antigen variants

Human Leukocyte Antigen Genetic Variations in Obstructive Sleep Apnea Patients that were positive for HLA-DQB1*0602.

Comprehensive Analysis of N6-Methyladenosine Regulators in the Subcluster Classification and Drug Candidates Prediction of Severe Obstructive Sleep Apnea

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The association of HLA-DQB1*0602 but not HLA-DRB1*15 with obstructive sleep apnea

Abstract: The presence of HLA-DQB1*0602 allele, but not HLA-DRB1*15 allele, was significantly associated with OSA.

Cited by 3 publications

References 47 publications

Relationship between obstructive sleep apnea and human leukocyte antigen variants

Relationship between obstructive sleep apnea and human leukocyte antigen variants

Human Leukocyte Antigen Genetic Variations in Obstructive Sleep Apnea Patients that were positive for HLA-DQB1*0602.

Comprehensive Analysis of N6-Methyladenosine Regulators in the Subcluster Classification and Drug Candidates Prediction of Severe Obstructive Sleep Apnea

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Product

Resources

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The association of HLA-DQB10602 but not HLA-DRB115 with obstructive sleep apnea

Abstract: The presence of HLA-DQB10602 allele, but not HLA-DRB115 allele, was significantly associated with OSA.