Study Of MOG1Variation With Atrial Fibrillation In A Chinese Han Population

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The mechanisms forthe development and maintainance of atrial fibrillation are complicated. Linkage analysisof AF family showed many pathogenic genes and chromosomal regions. Due to the rareAF family, these genes can explain only a part of the AF pathogenesis. EpidemiologicalStudies showed that AF has inheritance tendency, and was affected by numerous riskfactors. The genes，environments，genes and environments interaction lead to the complexdiseases. Research methods of this complex diseases are candidate gene associationstudies， candidate gene mutation screening and genome-wide association studies(GWAS).The AF candidate gene approach relies on a relevant prior hypothesis，like ionchannel-encoding genes, genes regulate cardiac conduction disorders and automaticity.Several ion channel-encoding genes have been associated with AF.The genes encoding Nav1.5and Nav1.5regulatory proteins have been found to bemutated in patients with inherited forms of AF. Recently, MOG1was described as a newpartner of Nav1.5. MOG1interacts with Nav1.5, regulates the surface expression of Nav1.5.In this study, we tested whether MOG1could be a relevant candidate gene within an AFcohort. We performed a genetic screening of MOG1in480Chinese HAN patients with AFby High-resolution melting (HRM). Two new variations, nonsense variant c.103C>T（p.Q35X）and missense mutation c.287G>A（p.R96K）in two patients withAF but not in576controls.We constructed the recombinant plasmid pDsRed1-N/MOG1expressing a fusionconstruction of red fluorescent protein pDsRed1-N and MOG1and observe the nucleiclocalization of MOG1in HeLa cells. Transfecting pDsRed1-N1-MOG1（WT）,pDsRed1-N1-MOG1（p.Q35X）,pDsRed1-N1-MOG1（p.R96K）into HeLa cells. We foundcells failed to express red fluorescent protein due to the nonsense variant in MOG1 （p.Q35X）. The localization between MOG1（WT）and MOG1（p.R96K）was no obviousdifference in HeLa cells.