Effect of a GFOD2 variant on responses in total and LDL cholesterol in Mexican subjects with hypercholesterolemia after soy protein and soluble fiber supplementation

• Blood lipids levels depend on the diet-gene interaction.
• Gene variant for binding seed site of miRNA can modulate blood lipids.
• The variant in the miRNA seed site of the GFOD2 gene was associated with blood lipids.
• Subjects with the minor allele respond better to a dietary supplement to reduce blood lipids.
• Gene variants can identify highly responsive subjects to dietary treatments.

BackgroundAlthough dietary treatments can successfully reduce blood lipids in hypercholesterolemic subjects, individual variation in that response has on occasion been linked to allelic differences. SNP rs12449157 has shown association with HDL-C concentrations in GWAS and falls in the glucose-fructose oxidoreductase domain containing 2 (GFOD2) locus. Of interest, previous data suggest that this SNP may be under environmentally driven selection. Thus, the aim of this study was to assess if rs12449157 may mediate the response of lipid traits to a dietary supplementation (DS) with soy protein and soluble fiber in a Mexican population with hypercholesterolemia.MethodsForty-one subjects with hypercholesterolemia were given a low saturated fat diet (LSFD) for 1 month, followed by a LSFD + DS that included 25 g of soy protein and 15 g of soluble fiber (S/SF) daily for 2 months. Anthropometric, clinical, biochemical and dietary variables were determined. We analyzed the gene–diet interaction between the GFOD2 genotype, with the minor allele frequency of 0.24, and the DS on total cholesterol (TC) and LDL-C concentrations.ResultsHypercholesterolemic subjects with GFOD2 rs12449157 G allele had higher serum TC and LDL-C at the baseline and showed a greater response to the LSCD + S/SF (− 83.9 and − 57.5 mg/dl, respectively) than those with GFOD2 AA genotype (− 40.1 and − 21.8 mg/dl, respectively) (P = 0.006 for TC, 0.025 for LDL-C, respectively).ConclusionThe observed differences in allele-driven, diet-induced changes in blood lipids may be the result of a recent environmentally driven selection on the rs12449157 minor allele. Variation in the GFOD2 gene contributes to the genetic basis for a differential response to a cholesterol- or lipid-lowering diet.