Gene-nutrient interactions in the metabolic syndrome: single nucleotide polymorphisms in ADIPOQ and ADIPOR1 interact with plasma saturated fatty acids to modulate insulin resistance.
BACKGROUND
Progression of the metabolic syndrome (MetS) is determined by genetic and environmental factors. Gene-environment interactions may be important in modulating the susceptibility to the development of MetS traits.


OBJECTIVE
Gene-nutrient interactions were examined in MetS subjects to determine interactions between single nucleotide polymorphisms (SNPs) in the adiponectin gene (ADIPOQ) and its receptors (ADIPOR1 and ADIPOR2) and plasma fatty acid composition and their effects on MetS characteristics.


METHODS
Plasma fatty acid composition, insulin sensitivity, plasma adiponectin and lipid concentrations, and ADIPOQ, ADIPOR1, and ADIPOR2 SNP genotypes were determined in a cross-sectional analysis of 451 subjects with the MetS who participated in the LIPGENE (Diet, Genomics, and the Metabolic Syndrome: an Integrated Nutrition, Agro-food, Social, and Economic Analysis) dietary intervention study and were repeated in 1754 subjects from the LIPGENE-SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) case-control study (http://www.ucd.ie/lipgene).


RESULTS
Single SNP effects were detected in the cohort. Triacylglycerols, nonesterified fatty acids, and waist circumference were significantly different between genotypes for 2 SNPs (rs266729 in ADIPOQ and rs10920533 in ADIPOR1). Minor allele homozygotes for both of these SNPs were identified as having degrees of insulin resistance, as measured by the homeostasis model assessment of insulin resistance, that were highly responsive to differences in plasma saturated fatty acids (SFAs). The SFA-dependent association between ADIPOR1 rs10920533 and insulin resistance was replicated in cases with MetS from a separate independent study, which was an association not present in controls.


CONCLUSIONS
A reduction in plasma SFAs could be expected to lower insulin resistance in MetS subjects who are minor allele carriers of rs266729 in ADIPOQ and rs10920533 in ADIPOR1. Personalized dietary advice to decrease SFA consumption in these individuals may be recommended as a possible therapeutic measure to improve insulin sensitivity. This trial was registered at clinicaltrials.gov as NCT00429195.
Ferguson
Jane F
JF
University College Dublin, Dublin, Ireland.
Phillips
Catherine M
CM
Tierney
Audrey C
AC
Pérez-Martínez
Pablo
P
Defoort
Catherine
C
Helal
Olfa
O
Lairon
Denis
D
Planells
Richard
R
Shaw
Danielle I
DI
Lovegrove
Julie A
JA
Gjelstad
Ingrid Mf
IM
Drevon
Christian A
CA
Blaak
Ellen E
EE
Saris
Wim Hm
WH
Leszczynska-Golabek
Iwona
I
Kiec-Wilk
Beata
B
Risérus
Ulf
U
Karlström
Brita
B
Miranda
José Lopez-
JL
Roche
Helen M
HM
D052242:Adiponectin / Q000235:genetics*; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004041:Dietary Fats / Q000097:blood*; D018450:Disease Progression; D005227:Fatty Acids / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006720:Homozygote; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D054419:Receptors, Adiponectin / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference / Q000235:genetics
D052242:Adiponectin; D004041:Dietary Fats; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D054419:Receptors, Adiponectin; D014280:Triglycerides