👤 Sara Cheraghi

Obesity is a significant health issue worldwide, progressing due to genetic factors and lifestyle. Melanocortin 4 receptor (MC4R) gene polymorphisms have been identified as a cause of overweight and obesity risk. The aim of this study was a comprehensive assessment of MC4R polymorphism effects on overweight/obesity risk. All retrieved literature from PubMed, Web of Science and Scopus according to PRISMA guidelines up to June 2022 was reviewed. Inclusion criteria are restricted to English-language, human case-control/cohort studies with genotype distributions of MC4R polymorphisms and their association with obesity and overweight in any geographic regions and age. The heterogeneity using the I-squared statistic (I In our study, 39 eligible studies with 43 697 overweight and obese cases and 52 272 normal weights were included. In mixed-age populations, rs17700633, rs17782313, rs11872992, rs12970134, rs2229616 and rs571312 were evaluated. The remarkable association was seen by rs17782313 and rs12970134 in the Homozygous model (OR = 1.73; 95% CI: 1.51, 1.98 and 1.74; 95% CI: 1.29; 2.35, respectively). In addition, rs17782313 and rs12970134 were found to be more strongly linked to overweight and obesity in Asian and European population groups, as determined by a subgroup analysis of the geographic regions. The present study confirms the high association of rs17782313 and rs12970134 with obesity and overweight in all age groups and geographic regions. However, further functional studies and high-population research on other MC4R SNPs must validate their role. Show less

Invasive non-functional pituitary adenomas (NFPAs) constitute 35% of NFPAs. Despite a relatively large body of molecular investigations on the invasiveness of NFPA, the underlying molecular mechanisms of invasiveness are yet to be determined. Herein, we aimed to provide an overview of gene/microRNA(miRNAs) expression alterations in invasive NFPA. This article describes a systematic literature review of articles published up to March 23, 2021, on the transcriptional alterations of invasive NFPA. Five digital libraries were searched, and 42 articles in total fulfilled the eligibility criteria. Pathway enrichment was conducted, and protein interactions among the identified deregulated genes were inferred. In total 133 gene/protein transcriptional alterations, comprising 87 increased and 46 decreased expressions, were detected in a collective number of 1001 invasive compared with 1007 non-invasive patients with NFPA. Deregulation of CDH1, PTTG1, CCNB1, SNAI1, SLUG, EZR, and PRKACB, which are associated with epidermal-mesenchymal transition (EMT), was identified. Moreover, six members of the angiogenesis pathway, i.e., VEGFA, FLT1, CCND1, CTNNB1, MYC(c-MYC), and PTTG1, were detected. SLC2A1, FLT1, and VEGFA were also recognized in the hypoxia pathway. Physical interactions of CTNNB1 with FLT1, CCND1, and EZR as well as its indirect interactions with VEGFA, MYC, CCNB1, and PCNA indicate the tight interplay between EMT, angiogenesis, and hypoxia pathways in invasive NFPAs. In addition, Hippo, JAK-STAT, MAPK, Wnt, PI3K-Akt, Ras, TGF-b, VEGF, and ErbB were identified as interwoven signaling pathways. In conclusion, invasive NFPA shares very common deregulated signaling pathways with invasive cancers. A large amount of heterogeneity in the reported deregulations in different studies necessitates the validation of the expressional changes of the suggested biomarkers in a large number of patients with invasive NFPA. Show less