Role of the DNA repair genes and in human fat distribution and lipid profiles.

INTRODUCTION

Regional fat distribution strongly relates to metabolic comorbidities. We identified the DNA repair genes and to be differentially expressed between human subcutaneous (SAT) and omental visceral adipose tissue (OVAT) depots. As increased DNA damage is linked to metabolic disease, we here sought to analyze whether depot-specific and expression is related to anthropometric and metabolic profiles of obesity. We further tested for different mRNA regulatory mechanisms by analyzing promoter DNA methylation and genotyped rs7350 in the locus.

RESEARCH DESIGN AND METHODS

Gene expression (OVAT n=48; SAT n=55) and DNA promoter methylation data (OVAT and SAT n=77) were extracted from an existing dataset as described elsewhere. Genotype data for the 3'untranslated region (3'UTR) variant rs7350 were generated by using the TaqMan genotyping system in 243 subjects of the same cohort. Statistical analyses were done using SPSS statistics software 24 and GraphPad Prism 6.

RESULTS

We identified being higher (p=0.002) and being less expressed (p=0.0001) in OVAT compared with SAT. Further, we observed positive interdepot correlations of OVAT and SAT for both (p=1×10) and mRNA levels (p=0.024). Depot-specific associations were observed for both genes' methylation levels with either high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides and/or with OVAT/SAT-ratio (all p<0.05). A significantly lower level of total cholesterol in minor A-Allele carriers of rs7350 compared with AG and GG carriers (p=0.001) was observed. Additionally, subjects carrying the A-allele showed lower SAT expression level (p=0.030).

CONCLUSION

Our results suggest a fat depot-specific regulation of and potentially mediated by both DNA methylation and genetic variation. Rs7350, DNA methylation and/or mRNA levels of and are related to lipid parameters. Further studies are warranted to evaluate the functional role of the DNA repair genes and in obesity and fat distribution.