ROCK1 is associated with non‐syndromic cleft palate

Abstract

During human organogenesis, neural crest cells (NCCs), a population of cells with migratory capacity, migrate from the dorsal surface of the neural tube to different regions of the embryo, where they differentiate into a broad range of cell types. 1 In vertebrates, the cranial NCC-derived mesenchyme contributes considerably to the development of the face and pharyngeal arches. 2 Orofacial development is a complex and delicate process, and craniofacial morphogenesis and palate formation occur through a well-orchestrated series of actions-including growth, expansion and fusion of the prominences-which is tightly controlled by the spatial and temporal signalling network. 3 Correct formation of the secondary palate is conditioned by the ability of cells to interact with neighbouring cells Abstract Background: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein. Methods:A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled. Results: The rs35996865-G allele was under-transmitted in cases of nsCP [P = .006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)]. Conclusion: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology. K E Y W O R D S association analysis, cleft palate, orofacial malformation, ROCK1 168 |

Non-syndromic Cleft Palate: An Overview on Human Genetic and Environmental Risk Factors

“…ROCK regulates stress fiber and focal adhesion assembly (Phillips et al, 2012) and modulates cytoskeleton organization by phosphorylating different substrates, mainly myosin light chain and myosin phosphatase, involved in the contractility pathway that leads to normal palate development. A recent family-based association study carried out in two cohorts from Italy and Iran, showed a significant level of association between ROCK1 rs35996865-G and NSCPO (Palmieri et al, 2020). Currently, there are no reports demonstrating the involvement of ROCK2 in the onset of orofacial cleft, however, some studies show that the loss of both chromosome 18q and 2p (where ROCK1 and ROCK2 reside, respectively) determines a series of anomalies including defects of the palate and micrognathia (Suzuki et al, 2016).…”

Evaluation of the rs35996865 polymorphism of the ROCK1 gene in sepsis

“…The rs35996865 polymorphism located in the ROCK1 promoter region, about 2 kb upstream of the transcription start site. However, it is not known whether this polymorphism is able to alter the expression level of the ROCK1 gene 17 . There are only small numbers of studies related to this polymorphism.…”

“…There are only small numbers of studies related to this polymorphism. The ROCK1 gene rs35996865 polymorphism mapping to the 5ʹ-UTR has been reported to be significantly associated with colorectal cancer 18,19 , obesity-related metabolic syndrome 20 , renal cell carcinoma 21 , respiratory distress syndrome 22 , nonsyndromic cleft palate 17 , and systemic sclerosis 23 , but not with Behçet's disease 24 or Alzheimer's disease 25 . Although no association of this polymorphism was noted with primary open-angle glaucoma in a Turkish population 26 , this variant is nominally associated with risk of high-tension glaucoma in a Korean population 27 .…”

Evaluation of the Rho-kinase gene expression and polymorphisms in adult patients with acute appendicitis: a differential impact of gender

“…The rs35996865 polymorphism is located in the ROCK1 promoter region, about 2 kb upstream of the transcription start site. However, it is not known whether this polymorphism is able to alter the expression level of the ROCK1 gene 6 . The ROCK1 gene rs35996865 variant mapping to the 5ʹ-UTR has been reported to be markedly associated with obesity-related metabolic syndrome 7 , respiratory distress syndrome 8 , and nonsyndromic cleft palate 6 , but not with sepsis 9 or primary open-angle glaucoma 10 .…”

“…However, it is not known whether this polymorphism is able to alter the expression level of the ROCK1 gene 6 . The ROCK1 gene rs35996865 variant mapping to the 5ʹ-UTR has been reported to be markedly associated with obesity-related metabolic syndrome 7 , respiratory distress syndrome 8 , and nonsyndromic cleft palate 6 , but not with sepsis 9 or primary open-angle glaucoma 10 . The result of our study showed that there was no association between the rs35996865 variant and AA.…”