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Rui-zhi Zeng,1 Xiao-dan Lv,2 Geng-feng Liu,1 Guang-li Gu,1 Shi-quan Li,1 Lan Chen,1 Jun-hua Fan,1 Zhao-liang Liang,1 Hui-qin Wang,1 Fei Lu,1 Ling-ling Zhan,2 Xiao-ping Lv1 1Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Xiao-ping LvDepartment of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, No. 6 of Shuangyong Street, Qingxiu District, Nanning, 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86 135 1788 8390Email pingping98987@111.comObjective: To analyze the correlation between site rs962917 of the MYO9B gene and inflammatory bowel disease (IBD) in the Guangxi Zhuang nationality population.Methods: The intestinal mucosa tissue of 153 IBD subjects (Han and Zhuang patients only) in the Guangxi Zhuang autonomous region comprised the case group, and the intestinal mucosa tissue of 155 healthy subjects (Han and Zhuang patients only) in the same region represented the control group. Deoxyribonucleic acid was extracted from the intestinal mucosa tissue of each experimental group, and the MYO9B gene-target fragment containing the single nucleotide polymorphism (SNP) site rs962917 was designed. Finally, polymerase chain reaction products were obtained by amplification, analyzed, and compared using the sequencing results.Results: The results indicated that the genotype frequency of the MYO9B SNP site rs962917 between Crohn’s disease (CD) and control groups of Zhuang and Han participants differed significantly (P < 0.05). Furthermore, the genotype frequency of MYO9B site rs962917 differed significantly between the Zhuang and Han population groups (P < 0.05).Conclusion: Site rs962917 of the MYO9B gene is related to CD susceptibility and incidence among the Guangxi Zhuang population.Keywords: inflammatory bowel disease, IBD, ulcerative colitis, UC, Crohn’s disease, CD, MYO9B gene, gene polymorphism

Celiac disease (CD) patients present a loss of intestinal barrier function due to structural alterations in the tight junction (TJ) network, the most apical unions between epithelial cells. The association of TJ-related gene variants points to an implication of this network in disease susceptibility. This work aims to characterize the functional implication of TJ-related, disease-associated loci in CD pathogenesis. We performed an association study of 8 TJ-related gene variants in a cohort of 270 CD and 91 non-CD controls. The expression level of transcripts located in the associated SNP region was analyzed by RT-PCR in several human tissues and in duodenal biopsies of celiac patients and non-CD controls. (si)RNA-driven silencing combined with gliadin in the Caco2 intestinal cell line was used to analyze the implication of transcripts from the associated region in the regulation of TJ genes. We replicated the association of rs6962966*A variant [p = 0.0029; OR = 1.88 (95%1.24-2.87)], located in an intron of TJ-related MAGI2 coding gene and upstream of RP4-587D13.2 transcript, bioinformatically classified as a long non-coding RNA (lncRNA). The expression of both genes is correlated and constitutively downregulated in CD intestine. Silencing of lncRNA decreases the levels of MAGI2 protein. At the same time, silencing of MAGI2 affects the expression of several TJ-related genes. The associated region is functionally altered in disease, probably affecting CD-related TJ genes. This work was partially funded by the Basque Department of Education grant IT1281-19 and ISCIII Research Project PI16/00258, cofunded by the European Union ERDF, A way to make Europe to JB. AC-R is supported by an Ikerbasque Fellowship and funded by a research project grant 2017111082 from the Basque Goverment. IS was funded by a research project grant 2015111068 from the Basque Department of Health. AJ-M and AO-G are predoctoral fellows funded by FPI grants from the Basque Department of Education, Universities and Research and IR-G and MS are predoctoral fellows funded by the University of Basque Country.

Introduction: the MYO9B gene contributes to the maintenance of the intestinal barrier and it has been postulated as a risk factor of celiac disease (CD). The objective of this study was to compare the frequency and association rs2305764, rs2305767and rs1457092 MYO09B polymorphisms in pediatric CD patients from Chile and Argentina. Patients and methods: the study was made in 104 CD pediatric patients (Chilean and Argentineans) and 104 controls subjects. MYO9B gene polymorphisms were analyzed by Taqman allelic probes. We evaluated the Hardy-Weinberg equilibrium by means of Chi-square and compared the haplotypes distribution using Fisher test. Results: SNPs rs2305767 and rs1457092 were associated with celiac disease (CD); TT genotype in rs2305767 would be a protective factor (p < 0.000, OR = 0.19 CI 0.1-0.4) and the CT genotype would be a risk factor (p < 0.0001, OR = 4.9 CI 2.2 to 11.3). CC genotype in rs1457092 also showed a protective effect for celiac (p < 0.000, OR = 0.07 CI 0.0 to 0.3). Conclusion: our findings suggest that genetic variation MYO9B gene is associated with CD, as a protective or a risk factor depending on the polymorphism studied.