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标题：Genetic association study of NOD2 and IL23R amino acid substitution polymorphisms in Saudi Inflammatory Bowel Disease patients
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作者：Raneem Saadi Alharbi ; Raneem Saadi Alharbi ; Noor Ahmad Shaik 等
期刊名称：Journal of King Saud University - Science
印刷版ISSN：1018-3647
出版年度：2022
卷号：34
期号：1
页码：1-9
DOI：10.1016/j.jksus.2021.101726
语种：English
出版社：Elsevier
摘要：AbstractBackgroundInflammatory Bowel Disease (IBD) is a complex autoimmune disease whose genetic basis is not well explored in the highly consanguineous Saudi population. Therefore, this study aims to evaluate the relevance ofNOD2andIL23Rgenes polymorphisms, selected from Caucasian Genome-wide association study (GWAS) findings, as risk markers for IBD pathology in Saudi patients.Materials and MethodsThe genetic status ofNOD2and IL23R polymorphisms of 97 IBD patients and 100 healthy individuals was determined through real-time PCR based TaqMan Allelic Discrimination Assay. Genotype calls of TaqMan assay were further validated by the direct DNA sequencing method. The pathogenicity of the variants was further explored by computational predictions and by 3D structural modelling methods.ResultsOur study found no evidence for a significant association of Caucasian IBD risk alleles, i.e., NOD2 (P268S and R702W) and IL23R (G149R and R381Q) with IBD pathology in Saudi Arabian patients under dominant, recessive or co-dominant genetic models. Moreover, SNP-SNP interaction analysis with multidimensionality reduction assays have also confirmed the above findings. Our computational predictions of the variants suggest the variable deleterious nature and minor structural drifts on the tertiary protein structures.ConclusionThis study expands the genetic heterogeneity of IBD and concludes that Caucasian genetic risk markers have limited or of no use in estimating the risk of IBD development in Saudi patients. Future genetic association studies in Saudi Arabia need to employ genetic markers whose minor allele frequencies exceed 10% in Arab population to have robust outcomes.
关键词：NOD2;IL23R;Inflammatory Bowel Disease;Crohn’s disease;Polymorphism