Association of IRF6 rs2235371 Polymorphism with Non-Syndromic Cleft Lip/Palate: A Meta-analysis

Background: The previous published data on the association between interferon regulatory factor 6 (IRF6) polymorphisms and non-syndromic Cleft Lip/Palate (NSCL ± P) risk remained inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations. Methods: A comprehensive search in PubMed, EMBASE, Web of Science, and CNKI for all eligible studies up July 2021. Results: A total of 23 studies with 6,161 cases and 8,919 controls were selected for this meta-analysis. Overall pooled analysis suggest a significant association between IRF6 rs2235371 polymorphism and CL±P risk under all the five genetic models, i.e., allele (A vs. G: OR=0.754, 95% CI 0.628-0.905, P=0.002), homozygote (AA vs. GG: OR=0.621 95% 0.405-0.953, P=0.029), heterozygote (AC vs. GG: OR=0.619, 95% CI 0.485-0.791, P≤0.001), dominant (AA+AG vs. GG: OR=0.550, 95% CI 0.381-0.794, P=0.001) and recessive model (AA vs. AG+GG: OR=0.583, 95% CI 0.423-0.804, P=0.001). Subgroup analysis by ethnicity showed that rs2235371 was associated with NSCL±P risk in Asians. Conclusion: This meta-analysis provides strong evidences that IRF6 rs2235371 might be associated with risk of NSCL ± P.

“VAN DER WOUDE SYNDROME: REPORT OF TWO CASES”

Van Der Woude syndrome is a rare autosomal dominant condition which is associated with developmental malformations involving lips, palate. This syndrome can be a genetic origin due to Microdeletion of chromosome bands 1q32-q41 and also mutation of Interferon regulatory factor 6 (IRF-6) can be a pathogenic cause. We report two interesting cases of Van Der Woude syndrome with lip pits and orofacial features.

IRF6 Genetic Variation and Maternal Smoking During Pregnancy in Cleft Lip/Palate

The goal of the present work was to revisit published data to test if genetic variation in interferon regulatory factor 6 (IRF6) is associated with children born with cleft lip with or without cleft palate (CL/P) for cases with positive history of maternal smoking. From the 573 individuals originally studied, this reanalysis focused on 57 who had a positive history of maternal smoking during pregnancy (39 born with CL/P and 18 born without CL/P). Seven IRF6 markers (rs4844880, rs2235371, rs2013162, ra861019, rs2073487, rs642961, and rs658860) were tested for over-transmission of alleles and an alpha of 0.05 was considered statistically significant. All individuals born with CL/P were homozygous for the wild type allele of rs2235371 in comparison to just two individuals born without clefts (p = 0.0000001). For rs861019, individuals born with CL/P were more likely to have the variant allele (p = 0.006). A similar trend was seen for rs642961 (p = 0.09). The results suggest that statistical evidence of over-representation of IRF6 alleles in individuals born with CL/P may be unveiled only when maternal smoking during pregnancy is used as the inclusion criterion in the analysis.

A Network Pharmacology Exploring the Mechanism of a Chinese Medicine Pair for the Treatment of Gout

Background:Gout is a crystalline-related arthropathy aroused by monosodium urate aggradation, which directly have a bearing on the disturbance of purine excretory and/or hyperuricemia, and seriously affects human health. In China, Dioscoreae Hypoglaucae Rhizoma (DH) and Smilacis Glabrae Rhixoma (SG) are widely used as medicinal pairs to prevent and treat gout. However, there is still a lack of research on the mechanism of DS (DH and SG). The aim of this study is to identify the absorbable components, potential targets and related therapeutic pathways of DS by means of network pharmacology.Material/Methods:We searched the effective chemical components of DS from TCMSP database, and explored the target of DS from GeneCards, a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) and STITCH database. Databases such as Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGkb) were used to query treatment targets for gout. Cytoscape software was applied to build the network map, KEGG database was applied to analyze the pathway of action, and finally a multi-component-multi-target-multi-channel DS treatment gout network was formed.Results: We found 16 active components, 24 KEGG metabolic pathways and 47 common targets of DS. The herb couple DS shares 9 targets with gout, including NOD like receptor protein 3 (NLRP3), Steryl-sulfatase (STS), Ephrin type-B receptor 2 (EPHB2), 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1), ROS Proto-Oncogene 1, Receptor Tyrosine Kinase (ROS1), Solute carrier family 22 member 12 (SLC22A12), Phospholipid-transporting ATPase IB (ATP8A2), Interferon regulatory factor 6 (IRF6) and P2X purinoceptor 7 (P2RX7), which may be the key point of DS in the treatment of gout.Conclusions:In this study, we tried to explain the mechanism of DS in the prevention and treatment of gout by using the network pharmacological method and provided an alternative way to study the effect of this Chinese medicine pair.

Expression of the interferon regulatory factor 6 in non-small cell lung carcinoma distinguishes squamous cell lung carcinoma from adenocarcinoma.

Non-small cell lung cancer, classified as adenocarcinomas or squamous cell lung carcinomas, is the major cause of cancer death in the United States and worldwide (1). To understand the most significant transcriptional differences between adenocarcinomas and squamous cell lung carcinomas, we mined published microarray data from two separate studies (2, 3). We identified interferon regulatory factor 6 (IRF6) as a distinguishing transcriptional feature of squamous cell lung carcinomas, suggesting the biology of IRF6 may be relevant to the pathways critical for the development or maintenance of squamous cell lung carcinomas but not of adenocarcinomas. IRF6 expression was significantly correlated with prognosis of patients with NSCLC, as patients with low tumor expression of IRF6 possessed significantly longer median overall survival than those with high tumor expression of IRF6. These analyses will also provide novel tools for diagnostic approaches and for guidance of treatment regimens for a cancer with dismal outlook.