Phospholipid Biosynthesis Genes and Susceptibility to Obesity: Analysis of Expression and Polymorphisms

Abstract

Recent studies have identified links between phospholipid composition and altered cellular functions in animal models of obesity, but the involvement of phospholipid biosynthesis genes in human obesity are not well understood. We analyzed the transcript of four phospholipid biosynthesis genes in adipose and muscle from 170 subjects. We examined publicly available genome-wide association data from the GIANT and MAGIC cohorts to investigate the association of SNPs in these genes with obesity and glucose homeostasis traits, respectively. Trait-associated SNPs were genotyped to evaluate their roles in regulating expression in adipose. In adipose tissue, expression of PEMT, PCYT1A, and PTDSS2 were positively correlated and PCYT2 was negatively correlated with percent fat mass and body mass index (BMI). Among the polymorphisms in these genes, SNP rs4646404 in PEMT showed the strongest association (p = 3.07E-06) with waist-to-hip ratio (WHR) adjusted for BMI. The WHR-associated intronic SNP rs4646343 in the PEMT gene showed the strongest association with its expression in adipose. Allele “C” of this SNP was associated with higher WHR (p = 2.47E-05) and with higher expression (p = 4.10E-04). Our study shows that the expression of PEMT gene is high in obese insulin-resistant subjects. Intronic cis-regulatory polymorphisms may increase the genetic risk of obesity by modulating PEMT expression.

Genome-wide association study of milk fatty acid composition in Italian Simmental and Italian Holstein cows using single nucleotide polymorphism arrays

“…PCYT2 encodes ethanolamine-phosphate cytidylyltransferase 2 involved in the synthesis of phosphatidylethanolamine from diacylglycerol. In human adipose tissue, PCYT2 expression is negatively correlated with fat mass percentage and body mass index (Sharma et al, 2013). In this regard, it is interesting that both genes are on BTA19 and closely linked to FASN, separated by only ~63.1 and ~122.8 kb, respectively.…”

Genome-wide association between single nucleotide polymorphisms with beef fatty acid profile in Nellore cattle using the single step procedure

“…The first, BTA1 at 71 Mb has three associated genes: SLC51A , PCYT1A , and TCTEX1D2 . The main candidate is PCYT1A , which is a protein-coding gene controlling the phosphatidylcholine, a phospholipid emulsifier with detergent action that reduces surface tension, forming smaller fat particles as triglycerides [ 42 ] and has been related to fat percentage and body mass index in humans [ 43 ].…”

Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals

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