title: Variation in the FFAR1 gene modifies BMI, body composition and beta-cell function in overweight subjects: an exploratory analysis.
abstract: BACKGROUND
  FFAR1 receptor is a long chain fatty acid G-protein coupled receptor which is expressed widely, but found in high density in the pancreas and central nervous system. It has been suggested that FFAR1 may play a role in insulin sensitivity, lipotoxicity and is associated with type 2 diabetes. Here we investigate the effect of three common SNPs of FFAR1 (rs2301151; rs16970264; rs1573611) on pancreatic function, BMI, body composition and plasma lipids.
  
  
  RESULTS
  For this enquiry we used the baseline RISCK data, which provides a cohort of overweight subjects at increased cardiometabolic risk with detailed phenotyping. The key findings were SNPs of the FFAR1 gene region were associated with differences in body composition and lipids, and the effects of the 3 SNPs combined were cumulative on BMI, body composition and total cholesterol. The effects on BMI and body fat were predominantly mediated by rs1573611 (1.06 kg/m(2) higher (P = 0.009) BMI and 1.53% higher (P = 0.002) body fat per C allele). Differences in plasma lipids were also associated with the BMI-increasing allele of rs2301151 including higher total cholesterol (0.2 mmol/L per G allele, P = 0.01) and with the variant A allele of rs16970264 associated with lower total (0.3 mmol/L, P = 0.02) and LDL (0.2 mmol/L, P<0.05) cholesterol, but also with lower HDL-cholesterol (0.09 mmol/L, P<0.05) although the difference was not apparent when controlling for multiple testing. There were no statistically significant effects of the three SNPs on insulin sensitivity or beta cell function. However accumulated risk allele showed a lower beta cell function on increasing plasma fatty acids with a carbon chain greater than six.
  
  
  CONCLUSIONS
  Differences in body composition and lipids associated with common SNPs in the FFAR1 gene were apparently not mediated by changes in insulin sensitivity or beta-cell function.
authors.affiliation: Elsie Widdowson Laboratory, MRC Human Nutrition Research, Cambridge, United Kingdom.
authors.forename: Celia G
authors.initials: CG
authors.lastname: Walker
authors.forename: Louise
authors.initials: L
authors.lastname: Goff
authors.forename: Les J
authors.initials: LJ
authors.lastname: Bluck
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Griffin
authors.forename: Susan A
authors.initials: SA
authors.lastname: Jebb
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Thomas A B
authors.initials: TA
authors.lastname: Sanders
authors.forename: Gary S
authors.initials: GS
authors.lastname: Frost
mesh_terms: D001823:Body Composition / Q000235:genetics*; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D050177:Overweight / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*
chemical_list: C473034:FFAR1 protein, human; D007328:Insulin; D008055:Lipids; D043562:Receptors, G-Protein-Coupled