title: Leptin receptor polymorphisms interact with polyunsaturated fatty acids to augment risk of insulin resistance and metabolic syndrome in adults.
abstract: The leptin receptor (LEPR) is associated with insulin resistance, a key feature of metabolic syndrome (MetS). Gene-fatty acid interactions may affect MetS risk. The objective was to investigate the relationship among LEPR polymorphisms, insulin resistance, and MetS risk and whether plasma fatty acids, a biomarker of dietary fatty acids, modulate this. LEPR polymorphisms (rs10493380, rs1137100, rs1137101, rs12067936, rs1805096, rs2025805, rs3790419, rs3790433, rs6673324, and rs8179183), biochemical measurements, and plasma fatty acid profiles were determined in the LIPGENE-SU.VI.MAX study of MetS cases and matched controls (n = 1754). LEPR rs3790433 GG homozygotes had increased MetS risk compared with the minor A allele carriers [odds ratio (OR) = 1.65; 95% CI: 1.05-2.57; P = 0.028], which may be accounted for by their increased risk of elevated insulin concentrations (OR 2.40; 95% CI: 1.28-4.50; P = 0.006) and insulin resistance (OR = 2.15; 95% CI: 1.18-3.90; P = 0.012). Low (less than median) plasma (n-3) and high (n-6) PUFA status exacerbated the genetic risk conferred by GG homozygosity to hyperinsulinemia (OR 2.92-2.94) and insulin resistance (OR 3.40-3.47). Interestingly, these associations were abolished against a high (n-3) or low (n-6) PUFA background. Importantly, we replicated some of these findings in an independent cohort. Homozygosity for the LEPR rs3790433 G allele was associated with insulin resistance, which may predispose to increased MetS risk. Novel gene-nutrient interactions between LEPR rs3790433 and PUFA suggest that these genetic influences were more evident in individuals with low plasma (n-3) or high plasma (n-6) PUFA.
authors.affiliation: Nutrigenomics Research Group, School of Public Health and Population Science, University College Dublin Conway Institute, University College, Dublin 4, Ireland.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Phillips
authors.forename: Louisa
authors.initials: L
authors.lastname: Goumidi
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bertrais
authors.forename: Martyn R
authors.initials: MR
authors.lastname: Field
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: L Adrienne
authors.initials: LA
authors.lastname: Cupples
authors.forename: Catherine
authors.initials: C
authors.lastname: Defoort
authors.forename: Julie A
authors.initials: JA
authors.lastname: Lovegrove
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
authors.forename: Ellen E
authors.initials: EE
authors.lastname: Blaak
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gibney
authors.forename: Beata
authors.initials: B
authors.lastname: Kiec-Wilk
authors.forename: Britta
authors.initials: B
authors.lastname: Karlstrom
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
authors.forename: Ross
authors.initials: R
authors.lastname: McManus
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.forename: Denis
authors.initials: D
authors.lastname: Lairon
authors.forename: Richard
authors.initials: R
authors.lastname: Planells
authors.forename: Helen M
authors.initials: HM
authors.lastname: Roche
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D015525:Fatty Acids, Omega-3 / Q000097:blood; D043371:Fatty Acids, Omega-6 / Q000097:blood; D005231:Fatty Acids, Unsaturated / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000209:etiology / Q000235:genetics*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D054411:Receptors, Leptin / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D007328:Insulin; D054411:Receptors, Leptin