Impact of NMT1 Gene Polymorphisms on Features of the Metabolic Syndrome among Severely Obese Patients

Abstract

Introduction: N-myristoyltransferase (NMT) is implicated in myristoylation, required for biological
activities of several proteins. Its gene N-myristoyltransferase 1 (NMT1) has been found
to be overexpressed and hypermethylated in Visceral Adipose Tissue (VAT) of severely obese
individuals with Metabolic Syndrome (MetS+) versus without (MetS-).
Objective: The aim of this study was to verify the associations between NMT1 gene polymorphisms
Single Nucleotide Polymorphisms (SNPs) and metabolic complications among obese
subjects.
Methods: Associations between SNPs and determinants of MetS were tested with 1752 obese
participants undergoing a bariatric surgery. The effect of selected SNPs on methylation, and
correlation with expression levels of NMT1 were verified in subgroups.
Results: Rs2239921 was significantly associated with systolic (p=0.03) and diastolic (p<0.0001)
blood pressures. Rs2239923 was associated with plasma High Density Lipoprotein-Cholesterol
or HDL-Cholesterol (HDL-C) levels (p=0.05), while rs2269746 was associated with Low Density
Lipoprotein-Cholesterol or LDL-Cholesterol (LDL-C) (p=0.006) and Total-Cholesterol
(Total-C) levels (p=0.004). Rs1005136 (p=0.03), rs8066395 (p=0.03) or rs2157840 (p=0.04)
were associated with plasma concentrations of C-Reactive Protein (CRP). Phenotype-associated
SNPs were associated with NMT1 methylation levels of six CpG sites. NMT1 methylation
levels of one CpG site, cg10755730, correlated with gene expression levels (r=0.57; p=0.04).
Conclusion: These results suggest that the presence of NMT1 SNPs is associated with altered
plasma lipid levels as well as with increased inflammation markers and blood pressure among
severely obese patients.