PMID- 34042155 OWN - NLM STAT- MEDLINE DCOM- 20220203 LR - 20240402 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 41 IP - 6 DP - 2021 Jun 25 TI - TagSNP approach for HLA risk allele genotyping of Saudi celiac disease patients: effectiveness and pitfalls. LID - 10.1042/BSR20210509 [doi] LID - BSR20210509 AB - BACKGROUND: Celiac disease (CD) is a genetically complex autoimmune disease which is triggered by dietary gluten. Human leukocyte antigen (HLA) class II genes are known to act as high-risk markers for CD, where >95% of CD patients carry (HLA), DQ2 and/or DQ8 alleles. Therefore, the present study was conducted to investigate the distribution of HLA haplotypes among Saudi CD patients and healthy controls by using the tag single nucleotide polymorphisms (SNP). METHODS: HLA-tag SNPs showing strong linkage value (r2>0.99) were used to predict the HLA DQ2 and DQ8 genotypes in 101 Saudi CD patients and in 103 healthy controls by using real-time polymerase chain reaction technique. Genotype calls were further validated by Sanger sequencing method. RESULTS: A total of 63.7% of CD cases and of 60.2% of controls were predicted to carry HLA-DQ2 and DQ8 heterodimers, either in the homozygous or heterozygous states. The prevalence of DQ8 in our CD patients was predicted to be higher than the patients from other ethnic populations (35.6%). More than 32% of the CD patients were found to be non-carriers of HLA risk haplotypes as predicted by the tag SNPs. CONCLUSION: The present study highlights that the Caucasian specific HLA-tag SNPs would be of limited value to accurately predict CD specific HLA haplotypes in Saudi population, when compared with the Caucasian groups. Prediction of risk haplotypes by tag SNPs in ethnic groups is a good alternate approach as long as the tag SNPs were identified from the local population genetic variant databases. CI - (c) 2021 The Author(s). FAU - Baaqeel, Reham H AU - Baaqeel RH AUID- ORCID: 0000-0002-3899-224X AD - Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Banaganapalli, Babajan AU - Banaganapalli B AD - Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. AD - Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Al Mahdi, Hadiah Bassam AU - Al Mahdi HB AD - Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. AD - Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Salama, Mohammed A AU - Salama MA AD - Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. AD - Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Alhussaini, Bakr H AU - Alhussaini BH AD - Pediatric Gastroenterology Unit, Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Alaifan, Meshari A AU - Alaifan MA AD - Pediatric Gastroenterology Unit, Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Bin-Taleb, Yagoub AU - Bin-Taleb Y AD - Pediatric Gastroenterology Unit, Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Shaik, Noor Ahmad AU - Shaik NA AD - Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. AD - Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Al-Aama, Jumana Yousuf AU - Al-Aama JY AD - Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. AD - Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Elango, Ramu AU - Elango R AUID- ORCID: 0000-0003-4264-2135 AD - Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. AD - Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia. FAU - Saadah, Omar I AU - Saadah OI AD - Pediatric Gastroenterology Unit, Department of Pediatrics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (HLA Antigens) SB - IM MH - Adult MH - Arabs/genetics MH - Case-Control Studies MH - Celiac Disease/diagnosis/ethnology/*genetics MH - Female MH - Gene Frequency MH - Genetic Predisposition to Disease MH - HLA Antigens/*genetics MH - Haplotypes MH - Humans MH - Male MH - Phenotype MH - *Polymorphism, Single Nucleotide MH - Predictive Value of Tests MH - Real-Time Polymerase Chain Reaction MH - Risk Assessment MH - Risk Factors MH - Saudi Arabia/epidemiology MH - Young Adult PMC - PMC8202064 OTO - NOTNLM OT - Celiac OT - Genetics OT - HLA Typing OT - autoimmunity COIS- The authors declare that there are no competing interests associated with the manuscript. EDAT- 2021/05/28 06:00 MHDA- 2022/02/04 06:00 PMCR- 2021/06/10 CRDT- 2021/05/27 08:54 PHST- 2021/02/28 00:00 [received] PHST- 2021/05/04 00:00 [revised] PHST- 2021/05/24 00:00 [accepted] PHST- 2021/05/28 06:00 [pubmed] PHST- 2022/02/04 06:00 [medline] PHST- 2021/05/27 08:54 [entrez] PHST- 2021/06/10 00:00 [pmc-release] AID - 228776 [pii] AID - BSR20210509 [pii] AID - 10.1042/BSR20210509 [doi] PST - ppublish SO - Biosci Rep. 2021 Jun 25;41(6):BSR20210509. doi: 10.1042/BSR20210509.