Coronavirus Vaccination and Mortality in the Omicron Outbreak in Iran: Mortality Reduction due to Attenuated Pathogenicity and Booster Vaccine Doses

en 35633987 Coronavirus Vaccination and Mortality in the Omicron Outbreak in Iran: Mortality Reduction due to Attenuated Pathogenicity and Booster Vaccine Doses More than two years after the first report of the rapidly spreading coronavirus disease 2019 (COVID-19), the coronavirus is still unpredictable by emerging highly divergent variants 1. Through the highly contagious viral sickness the virus causes, it imposes significant morbidity and mortality on global populations, becoming the second cause of death in people aged 25 to 44 years in January 2021 in the United States. Although mortality rates in disease peaks were significantly reduced as vaccination rates increased, mortality increased again with the outbreak of a variant of concern called Omicron so that the virus became the second leading cause of death in January 2022 in the United States 1,2. The novel variant, first identified in Botswana and named Omicron (B.1.1.529) by World Health Organization on November 26, 2021, exhibited 36 mutations in the spike protein, the target of antibodies, and a total of 59 mutations throughout its genome. More importantly, 15 mutations occurred in the Receptor-Binding Domain (RBD), which can increase infectivity and mediate virus escape from vaccine-induced antibodies 3. In other words, the highly mutated omicron variant can evade immunity in vaccinated individuals and is associated with vaccine breakthroughs 1,3. The Omicron has a 13-fold increase in viral infectivity, and compared to the Delta variant, it is 2.8 times more contagious and its R0, the indicator of contagiousness and transmissibility, can be as high as 10, while for the Delta, it did not reach 7 4. Fortunately, the mortality of this variant is lower than the wild type and Alpha, Beta and Delta variants 5. About two years after the first official report of the SARS-CoV-2 outbreak in Iran, like in other countries, the virus is still raging. As in other countries, the peak of the Omicron variant in Iran increased infection, hospitalization, and mortality once again. During the Omicron outbreak in Iran, the maximum number of newly identified cases in one day was more than 39,000, so that the maximum number of active cases in one day reached about 375,000 by mid-February 2022. Although in the previous peak, the maximum number of new cases detected in a day and the maximum number of deaths per day were about 50,000 and more than 700, respectively, the number of deaths per day did not reach 250 in this peak 6. This difference may be due to the lower mortality5 and progress of the vaccination process, although vaccine efficacy is negatively affected by new variants 3. Although the percentages of people who have received at least one dose of a vaccine, have been fully vaccinated, and given the booster dose are now about 75%, 65%, and 25%, respectively, these percentages on August 24, 2021, when the highest number of deaths due to COVID-19 were reported in Iran, were about 20%, 7%, and 0, respectively 7. The fastest and most accessible ways to protect against the Omicron variant seem to be wearing medical-grade masks and receiving the third dose of vaccine 8. The protection provided by two shots of vaccines is reduced to less than 40% a few months after the second shot, but the third shot seems to cause about 60 to 70% protection in the two weeks after the injection and protect against severe COVID-19 9. It has been shown that vaccine efficacy decreases with increasing time after vaccination 3. There is not much difference in the treatment of the disease caused by this variant, but of the monoclonal antibodies, only sotrovimab appears to be effective and is authorized 4. Eventually, updating the current vaccines and pursuing a universal vaccine should be of concern to those in charge 8,10. Coronavirus spike protein, COVID-19 Pandemic, Mass active immunization, SARS-CoV-2 102 103 https://www.ajmb.org/En/Article.aspx?id=60492 https://www.ajmb.org/PDF/En/FullText/60492.pdf AhmadShamabadiPsychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran 71806ShahinAkhondzadehPsychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran739

en 35633981 Cellular Therapy: The Hope for Covid-19 Coronaviruses (CoVs) are a group of very diverse viruses that cause a broad spectrum of diseases from mild to severe enteric, respiratory, systemic diseases, and common cold or pneumonia among humans and animals. This virus is associated with Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and lung disease that lead to Acute Respiratory Distress Syndrome (ARDS). In December 2019, researchers identified a novel coronavirus type, called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), which was associated with symptoms of high fever, dry cough, headache, diarrhea, and reduction of White Blood Cells (WBC). Coronavirus-associated acute respiratory disease was named Coronavirus Disease 19 (COVID-19). No proven treatment has been discovered for COVID-19 so far, but researchers are trying to find the best effective way to treat this disease. Therefore, therapeutic strategies that facilitate the recovery of COVID-19 patients and reduce life-threatening complications are urgently needed now. Today, Mesenchymal Stem Cells (MSCs) and their secretion are utilized as one of the most applied tools to treat various diseases such as inflammation and cancer. MSC-derived vesicles are rich in various growth factors, cytokines, and interleukins that are produced and secreted under different physiological or pathological conditions. These vesicles were considered a suitable and effective tool in regeneration medicine because of their high power in repairing damaged tissues and modulating immune responses. Recently, evidence has shown MSC-derived vesicles through reduced expression of pro-inflammatory cytokines could improve damaged tissues in COVID-19 patients. In addition to MSCs and MSC-derived exosomes, Natural Killer (NK) cells, T cells, and platelet lysates were used against viral infection. In this review, we tried to provide an overview of MSC secretion and immune cells for COVID-19 therapy. COVID-19, Mesenchymal stem cell , Natural killer cells, Platelet lyses, SARS-CoV-2 104 113 https://www.ajmb.org/En/Article.aspx?id=60493 https://www.ajmb.org/PDF/En/FullText/60493.pdf SimaNobariResearch Center for Molecular Medicine, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran91825MotaharehRezvanDepartment of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran91826FaribaDashtestaniInstitute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran41632MahdiehGangiDepartment of Biology, Payame Noor University, Taft, Iran91827HodaKeshmiri NeghabDepartment of Photo Healing and Regeneration, Medical Laser Research Center, Yara Institute, ACECR, Tehran, Iran41629

en 35633984 Designing a Multi-Epitope Antigen for Serodiagnosis of Strongyloides stercoralis Based on L3Nie.01 and IgG Immunoreactive Epitopes Background: Serological diagnosis of Strongyloides stercoralis  (S. stercoralis) is fre-quently challenging because of cross-reactivity with other parasitic nematodes. There-fore, it is necessary to introduce novel serological tests with high performance to properly diagnose this neglected parasitic infection. The purpose of the current study was to design a multi-epitope construct for the diagnosis of S. stercoralis. Methods: For the purpose of this study, first, highly antigenic segments and potential immunodominant epitopes of S. stercoralis were identified from two antigenic proteins, and then all of the selected parts were linked by an appropriate linker. Next, the physico-chemical features of the designed construct were analyzed. Then, tertiary structures of the construct were built and evaluated to find out the best one. Lastly, the amino acid sequence was reverse-translated and optimized for over-expression in Escherchia coli (E. coli). Results: The bioinformatic evaluation indicated that the designed protein construct could be hydrophilic, thermostable, and acidic and the estimated half-life was more than 10 hr in E. coli. Conclusion: According to the results of the study, the designed construct could be used as an efficient antigen in the ELISA system for serological diagnosis of human strong-yloidiasis. Antigens, Multi-epitopes, Serological diagnosis, Strongyloides stercoralis 114 124 https://www.ajmb.org/En/Article.aspx?id=60494 https://www.ajmb.org/PDF/En/FullText/60494.pdf AhmadMovahedpourStudent Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran91828Zohreh Mostafavi-PourAutophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran91829Bahador SarkariBasic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran91830Mortaza Taheri-AnganehCellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran91831Navid Nezafat Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran91832Amir Savardashtaki Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran91833YounesGhasemiPharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran1042

en 35633989 CpG-Containing Oligodeoxynucleotides and Freund Adjuvant in Combination with Alum Augment the Production of Monoclonal Antibodies Against Recombinant HBsAg Background: Adjuvants are essential to potentiate the immune response to inoculated antigens and play a central role in vaccine development. Alum is generally used as a classic adjuvant, although it does not stimulate proper immunity, and some of the immunized subjects have low or no antibody response. Efforts have been continued to find more efficient adjuvants for better antibody responses. In the present study, the efficacy of three formulations of adjuvants, i.e. Cysteine p Guanine Oligodeoxynucleotide (CpG ODN), alum, and Freund, in the production of monoclonal anti Hepatitis B Surface Antigen (HBsAg) antibodies was investigated. Methods: To immunize mice, regular hepatitis B vaccine containing recombinant HBsAg and alum was used with CpG ODN or Freund adjuvants, and splenocytes of hyperimmunized mice were fused with murine myeloma Sp2/0 cells. Positive hybridomas were selected by Enzyme-Linked Immunosorbent Assay (ELISA) using HBsAg as coating antigen followed by a limited dilution process. Results: The results showed that by using all three formulations of adjuvants, monoclonal antibody (mAb) specific to HBsAg was successfully generated. It was also found that the mice immunized with (HBsAg + Alum) + CpG had the highest concentration of antibody production in serum and hybridoma supernatants as well as positive clones. Based on these findings, the addition of CpG ODN also induced a higher antibody response compared with Complete Freund’s Adjuvant (CFA). Conclusion: Results of this study showed that CpG and Freund adjuvants could be efficient partners for alum in the immunization period of the process of monoclonal antibody production. Aluminum sulfate, Freund adjuvant, Hepatitis B surface antigens, Monoclonal antibodies 125 131 https://www.ajmb.org/En/Article.aspx?id=60495 https://www.ajmb.org/PDF/En/FullText/60495.pdf Mahsa Khayyati KohnehshahriDepartment of Cellular and Molecular Biotechnology, Institute of Biotechnology, Urmia University, Urmia, Iran91835Nowruz Delirezh Department of Cellular and Molecular Biotechnology, Institute of Biotechnology, Urmia University, Urmia, Iran91836Leili Aghebati Maleki Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran91837

en 35633983 The Inhibitory Effect of Thioridazine on adeB Efflux Pump Gene Expression in Multidrug-Resistant Acinetobacter baumannii Isolates Using Real Time PCR Background: The purpose of the present study was to investigate the antimicrobial effects of berberine and thioridazine, as well as their effect on the gene expression of the AdeABC efflux pump system in Multidrug-Resistant (MDR) Acinetobacter baumannii (A. baumannii) isolates. Methods: This study was carried out in five MDR clinical isolates of A. baumannii and a sample of standard strain (A. baumannii PTCC1797). The effect of Minimum Inhibitory Concentration (MIC) and the Minimum Bactericidal Concentration (MBC) of berberine, thioridazine, and ciprofloxacin alone and their combination on A. baumannii was evaluated by broth microdilution method. Also, their effect on the expression of adeB efflux pump gene was evaluated using real time PCR method.        Results: The MIC of thioridazine, berberine, ciprofloxacin+thioridazine, ciprofloxacin+ berberine, thioridazine+berberine, and ciprofloxacin+thioridazine+berberine on MDR A. baumannii isolates was 64, 256, 128, 256, 128, and 128 μg/ml, respectively. The results showed that treatment of strains with thioridazine alone and in combination with berberine and ciprofloxacin significantly (p<0.05) decreased the expression of adeB efflux pump gene. Conclusion: Due to the inhibitory effects of thioridazine on bacterial isolates and adeB efflux pump gene, this compound can be used as a potential antimicrobial agent against MDR A. baumannii. Acinetobacter baumannii, Ciprofloxacin, Gene expression, Real time polymerase chain reaction, Thioridazine 132 136 https://www.ajmb.org/En/Article.aspx?id=60496 https://www.ajmb.org/PDF/En/FullText/60496.pdf FereshtehAhmadi Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran91838Bahman Khalvati Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran91839Saba Eslami Shiraz University of Medical Sciences, Shiraz, Iran91840MehdiMirzaiiFaculty of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran1067Narges Roustaei Department of Epidemiology and Biostatistics, School of Health and Nutrition Sciences, Social Determinants of Health Research Center, Yasuj University of Medical Sciences, Yasuj, Iran91842Farzad Mazloomirad Student Research Committee, Yasuj University of Medical Sciences, Yasuj, Iran91843Seyed SajjadKhoramroozDepartment of Microbiology, School of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran31610

en 35633986 A Motif-Based Network Analysis of Regulatory Patterns in Doxorubicin Effects on Treating Breast Cancer, a Systems Biology Study Background: Breast cancer is the most common malignancy worldwide. Doxorubicin is an anthracycline used to treat breast cancer as the first treatment choice. Never-theless, the molecular mechanisms underlying the response to Doxorubicin and its side effects are not comprehensively understood so far. We used systems biology and bio-informatics methods to identify essential genes and molecular mechanisms behind the body response to Doxorubicin and its side effects in breast cancer patients. Methods: Omics data were extracted and analyzed to construct the protein-protein interaction and gene regulatory networks. Network analysis was performed to iden-tify hubs, bottlenecks, clusters, and regulatory motifs to evaluate crucial genes and molecular mechanisms behind the body response to Doxorubicin and its side effects. Results: Analyzing the constructed PPI and gene-TF-miRNA regulatory network showed that MCM3, MCM10, and TP53 are key hub-bottlenecks and seed proteins. Enrichment analysis also revealed cell cycle, TP53 signaling, Forkhead box O (FoxO) signaling, and viral carcinogenesis as essential pathways in response to this drug. Besides, SNARE interactions in vesicular transport and neurotrophin signaling were identified as pathways related to the side effects of Doxorubicin. The apoptosis in-duction, DNA repair, invasion inhibition, metastasis, and DNA replication are sug-gested as critical molecular mechanisms underlying Doxorubicin anti-cancer effect. SNARE interactions in vesicular transport and neurotrophin signaling and FoxO signaling pathways in glucose metabolism are probably the mechanisms responsible for side effects of Doxorubicin. Conclusion: Following our model validation using the existing experimental data, we recommend our other newly predicted biomarkers and pathways as possible mole-cular mechanisms and side effects underlying the response to Doxorubicin in breast cancer requiring further investigations. Breast cancer, Doxorubicin, Protein-protein interaction network, Regulatory motif, Systems biology 137 153 https://www.ajmb.org/En/Article.aspx?id=60497 https://www.ajmb.org/PDF/En/FullText/60497.pdf Zeinab Dehghan Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran91845Seyed Amir MirmotalebisohiCellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran91846MarziehSameniCellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran91847MaryamBazgiriDepartment of Animal Science, Agriculture and Natural Resources University of Khuzestan, Ahvaz, Iran91848HakimehZaliDepartment of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran91849

en 35633990 Bioinformatic Investigation of Micro RNA-802 Target Genes, Protein Networks, and Its Potential Prognostic Value in Breast Cancer Background: An increasing number of studies have suggested that unveiling the molecular network of miRNAs may provide novel therapeutic targets or biomarkers. In this study, we investigated the probable molecular functions that are related to microRNA-802 (miR-802) and evaluated its prognostic value in breast cancer utilizing bioinformatics tools. Methods: PPI network, pathway enrichment and transcription factor analysis were applied to obtain hub genes among overlapping genes of four miRNA target prediction databases. Prognosis value assessments and expression analysis of hub genes using bioinformatics tools, as well as their literature validation were performed.  Results: Our results showed a significant correlation of the miR-802 overexpression with poor patient survival rate (BC, p=2.7e-5). We determined 247 target genes significant for GO and KEGG terms. Analysis of TFs by TRUST showed that RUNX3, FOXO3, and E2F1 are possible TFs that regulate the miR-802 expression and target genes network. According to our analysis; 21 genes might have an important function in miR-802 molecular processes and regulatory networks. The result shows that among these 21 genes, 8 genes (CASC3, ITGA4, AGO3, TARDBP, MED13L, SF1, SNRPE and CRNKL1) are positively correlated with patient survival. Therefore these genes could be considered and experimentally evaluated as a prognostic biomarker for breast cancer. Conclusion: The comprehensive bioinformatics study on miR-802 target genes provided insight into miR-802 mediated pathways and processes. Furthermore, representing candidate target genes by prognostic values indicates the potential clinical application of miR-802 in breast cancer. Bioinformatics, Breast cancer, Cell cycle, miR-802, Prognosis, Wnt signaling 154 164 https://www.ajmb.org/En/Article.aspx?id=60498 https://www.ajmb.org/PDF/En/FullText/60498.pdf MaryamEiniDepartment of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran985Sepideh Parsi Department of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran91851MahmoudBaratiPasteur Institute of Iran, Tehran, Iran61733GolnazBahramaliPasteur Institute of Iran, Tehran, Iran824Marziyeh Alizadeh Zarei Gametogenesis Research Center, Kashan University of Medical Sciences, Kashan, Iran91854Jafar KianiDepartment of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran91855AsaadAzarnezhadLiver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran1035ArshadHosseiniDepartment of Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran1037

en 35633985 Association of Aberrant Promoter Methylation Changes in the Suppressor of Cytokine Signaling 3 (SOCS3) Gene with Susceptibility to Crohn's Disease Background: Growing evidence supports that changes in the methylation state of Inflammatory Bowel Disease (IBD)-associated genes could significantly alter levels of gene expression, potentially contributing to disease onset and progression. We supposed that alterations in DNA methylation status at promoter region within the suppressor of cytokine signaling 3 (SOCS3) gene in intestinal tissues may be involved in the susceptibility to Crohn's Disease (CD). Methods: DNA methylation status in the promoter region of the human SOCS3 gene of intestinal tissues from 15 patients with CD and 15 age- and sex-matched healthy controls were profiled using the real-time Quantitative Multiplex Methylation Specific PCR (QM-MSP) assay. Results: Based on methylation assay data profiling, we found that patients with CD showed a higher degree of methylation of the SOCS3 gene promoter region than did the healthy controls (unmethylated DNA in CD vs. healthy controls; 0.00048±0.0011 vs. 0.07±0.142, p<0.000). Conclusion: The data presented here demonstrate that aberrant methylation of the CpG islands within promoter regions of SOCS3 gene in colonic mucosa of CD was associated with mucosal inflammatory status, providing insights into the involvement of methylation could contribute to the initiation of the inflammatory process and development of CD. Crohn's disease, DNA methylation, Epigenetic, Immune regulation, SOCS3 165 169 https://www.ajmb.org/En/Article.aspx?id=60499 https://www.ajmb.org/PDF/En/FullText/60499.pdf GolshidSanatiDepartment of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran91857DavoodJafariImmunogenetics Research Network (IgReN), Universal Scientific Education and Research Network (USERN), Zanjan, Iran91858MehrdadNoruziniaDepartment of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran225NaserEbrahimi-DaryaniDepartment of Internal Medicine, Division of Gastroenterology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran180MohammadAhmadvandDepartment of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran91859ShahramTeimourianDepartment of Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran91860NimaRezaeiNetwork of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Boston, USA186

en 35633988 Strong Association of Polymorphism in SPRED2 Gene with Disease Susceptibility and Clinical Characteristics of Rheumatoid Arthritis in the Iranian Population Background: The high heritability of Rheumatoid Arthritis (RA) has been estimated from different studies. Recently, Genome-Wide Association Studies (GWAS) show a large number of Single Nucleotide Polymorphisms (SNPs) loci affecting susceptibility to RA. The rs934734 polymorphism in the SPRED2 gene is one of these loci. Studies have shown that the SPRED2 gene is involved in the regulation of inflammatory response, leukocyte infiltration, and local chemokine production. In the current study, the possible association between SNP rs934734 (intronic variant) in the SPRED2 gene with RA risk in the Iranian population was evaluated. Methods: One hundred fourteen RA patients and 120 healthy counterparts were recruited in this case-control study to evaluate rs934734 genotypes using the real-time PCR High Resolution Melting method (HRM). Results: Logistic regression analysis demonstrated that GG and AG genotypes compared with AA genotype increase the risk of RA (GG vs. AA; OR=4.61; 95%CI [2.21-9.35]; p<0.001 and AG vs. AA; OR=2.54; 95%CI [1.36-4.76]; p=0.004). Furthermore, subjects with allele G were more frequently affected with RA than subjects with A allele (OR=2.33; 95%CI [1.61-3.38]; p<0.001). Besides, in the patient group, there was a significant correlation between Erythrocyte Sedimentation Rate (ESR) and C-reactive protein (CRP) concentration with rs934734 polymorphism (p<0.05). Conclusion: Our findings suggest that rs934734 in SPRED2 strongly underlies RA development and is associated with clinicopathological characteristics of this disease. Autoimmune disease, Genotype, Iran, Rheumatoid arthritis, Single nucleotide polymorphisms 170 174 https://www.ajmb.org/En/Article.aspx?id=60500 https://www.ajmb.org/PDF/En/FullText/60500.pdf BahramPakzadDivision of Rheumatology, Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran61766HamedMoghadammaneshDivision of Rheumatology, Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran91861MansourSalesiDivision of Rheumatology, Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran61763RasoulSalehiDepartment of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran61765

en 35633991 Association of MTHFR, BMP4, TGFA and IRF6 Polymorphisms with Non-Syndromic Cleft lip and Palate in North Indian Patients Background: Non-Syndromic Cleft Lip and Palate (NSCL/P) is a multifactorial birth defect. The world-wide prevalence of NSCL/P is 1 in 1000 live births; it differs with race, ethnicity and gender. The aim of the present study was to find out the status of candidate gene polymorphisms in NSCL/P cases and its association in phenotype of the patients. Methods: We have screened five polymorphisms in four candidate genes MTHFR (rs1801133, rs1801131) BMP4 (rs17563), TGFA (rs1146297) and IRF6 (rs2235371) by restriction fragment length polymorphism and results were validated by Sanger sequencing. Our dataset consists of 200 NSCL/P cases and 200 healthy controls from the Indian population. Statistical data analysis was performed by SPSS software. Results: MTHFR (rs1801133), BMP4 (rs175563) and TGFA (rs11466297) gene polymorphisms showed significant association with NSCL/P and act as a risk factor in the Indian population (p=<0.05). However, MTHFR (rs1801131), and IRF6 (rs2235371) gene polymorphisms did not show significant association with NSCL/P in the Indian population. Conclusion: The result of the study suggests an association between MTHFR (rs1801133), BMP4 (rs175563) and TGFA (rs11466297) polymorphisms with NSCL/P in Indian population. BMP4, Indian population, IRF6, MTHFR, NSCL/P, TGFA 175 180 https://www.ajmb.org/En/Article.aspx?id=60501 https://www.ajmb.org/PDF/En/FullText/60501.pdf KapilAvasthiDepartment of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India91862AmitAgarwalDepartment of Burn and Plastic Surgery, Vivekananda Polyclinic and Institute of Medical Sciences (VPIMS), Lucknow 226007, India91863SaritaAgarwalDepartment of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS), Lucknow 226014, India91864

en 35633982 Association of rs2013162 and rs2235375 Polymorphisms in IRF6 Gene with Susceptibility to Non-Syndromic Cleft Lip and Palate Background: Non-syndromic cleft lip occurs by the interaction of environmental and genetic factors. The purpose of the current study was to analyze the association of Single Nucleotide Polymorphisms (SNPs) in IRF6 and NSCL/P in an Iranian population. Methods: A group of 105 children with NSCL/P and 185 normal controls were included in the current study. Genotyping of IRF6 rs2013162 and rs2235375 was performed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results: A substantial association of AA and CA genotypes in rs2013162 with the risk of NSCL/P (AA vs. CC; OR=2.36; 95%CI [1.05-5.29], p=0.004; and CA vs. CC; OR=0.47; 95%CI [0.28-0.79], p=0.018) was found. However, there were no important associations between A allele and risk of NSCL/P (p=0.980). According to logistic regression analysis results, subjects with GG genotype and G allele in rs2235375 polymorphism had increased risk of NSCL/P. Conclusion: The IRF6 polymorphisms are associated with the susceptibility to NSCL/P in Iranian population. IRF6, Non-syndromic cleft lip and palate, Orofacial clefts, Polymorphism 181 185 https://www.ajmb.org/En/Article.aspx?id=60502 https://www.ajmb.org/PDF/En/FullText/60502.pdf MasoumehSoleymaniGenetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran91865AsgharEbadifarDentofacial Deformities Research Center, Research Institute of Dental Sciences, Department of Orthodontics, Faculty of Dentistry, Shahid Behehsti University of Medical Sciences, Tehran, Iran891MaryamKhosraviGenetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran91866EmranEsmaeilzadehFetal Health Research Center, Hope Generation Foundation, Tehran, Iran91867Hamid RezaKhorram KhorshidPersonalized Medicine and Genometabolomics Research Center, Hope Generation Foundation, Tehran, Iran42