Genetic association study of NOD2 and IL23R amino acid substitution polymorphisms in Saudi Inflammatory Bowel Disease patients

Journal of King Saud University: Science

Jumana Yousuf Al-Aama¹  Babajan Banaganapalli²  Hadiah Almahdi²  Omar Ibrahim Saadah³  Raneem Saadi Alharbi³  Noor Ahmad Shaik³  Hadeel A. Alsufyani⁴  Ramu Elango⁵  Hanan Abdelhalim ElSokary⁶  Bassam Adnan Jamalalail⁶  Mahmoud H. Mosli⁶ 

[1] Inflammatory Bowel Disease Research Group, King Abdulaziz University, Jeddah, Saudi Arabia;Princess Al-Jawhara Al-Ibrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Genetic Medicine, Faculty of Medicine, King Abdulaziz University, Saudi Arabia;Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia;Department of Medical Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia;Princess Al-Jawhara Al-Ibrahim Centre of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia;

关键词: NOD2;    IL23R;    Inflammatory Bowel Disease;    Crohn’s disease;    Polymorphism;   

DOI  :  

来源: DOAJ

【 摘 要 】

Background: Inflammatory 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 of NOD2 and IL23R genes polymorphisms, selected from Caucasian Genome-wide association study (GWAS) findings, as risk markers for IBD pathology in Saudi patients. Materials and Methods: The genetic status of NOD2 and 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. Results: Our 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. Conclusion: This 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.

【 授权许可】

Unknown