Single nucleotide polymorphisms affecting phosphatidylcholine transport are associated with obesity

Obesity is an increasingly prevalent disease characterized by multiple metabolic derangements controlled by environmental and genetic factors. Lipid metabolism abnormalities are prevalent in obesity and can manifest in hepatic steatosis, elevated serum lipids, and impaired lipid transport. Mice with a deletion of a gene for the synthesis of phosphatidylcholine (PtdCho) gain less weight when fed a high fat diet. We examined whether humans with single nucleotide polymorphisms in genes related to PtdCho and choline metabolism are less likely to be obese. We genotyped 660 individuals from the Duke University Health Systems nonalcoholic fatty liver disease (NAFLD) Clinical Database and Blood/Tissue Repository for 364 SNPs in genes of choline metabolism, including 49 SNPs in ATP binding cassette, subfamily B, member 4 gene ( ABCB4 ). ABCB4 is a PtdCho flippase responsible for secreting PtdCho from liver into bile. A linear model was used to examine the relationship of these SNPs to body mass index (BMI). Eight ABCB4 SNPs were found to be significantly associated with BMI after adjustment for gender (false discovery rate adjusted p value < 0.05). These findings suggest a relationship between PtdCho metabolism and obesity that was previously unappreciated. Future studies will address additional metabolic and clinical parameters that could further explain these findings. This work is supported by NIH grant DK055865.