Table 4.
Selected studies analyzing sex-specific gene-diet interactions in determining different phenotypes.
| Author | Study Characteristics and Aims | Findings |
|---|---|---|
| Ordovas JM et al., 2002 [85] | Examined whether dietary fat modulates the association between the APOA1 G-A polymorphism and HDL-in men and women from the Framingham Study. | We found a significant gene-diet interaction associated with the APOA1 G-A polymorphism. In women carriers of the A allele, higher polyunsaturated fatty acid (PUFA) intakes were associated with higher HDL-cholesterol concentrations, whereas the opposite effect was observed in G/G women. |
| Ribalta J et al., 2005 [86] | Identification of gender-specific genetic influences on fasting and postprandial TG concentrations under typical living conditions in healthy, lean, normolipidemics. | An adverse combination of common alleles of the FABP-2, APOE, and PPARgamma genes in women increases their TGs to values comparable to those seen in men. Although this influence is not appreciable when studying fasting plasma TGs, it becomes apparent with use of a more sensitive index. |
| Méplan C et al., 2007 [87] | Analysis of polymorphisms in the selenoprotein P gene determine the response of selenoprotein markers to selenium (Se) supplementation in a gender-specific manner (the SELGEN study). | Two common functional SNPs within the human SePP gene that may predict behavior of biomarkers of Se status and response to supplementation and thus susceptibility to disease. Both SNPs and gender were associated with differences in scavenger glutathione peroxidase 3 (GPx3) activity and other markers. |
| Hu M et al., 2012 [88] | Intervention with a high-carbohydrate (high-CHO) diet for a short-term and investigation of the interactions with the hepatic lipase G-250A promoter polymorphism to affect the ratios of plasma lipids and apolipoproteins. | The high-CHO diet induced the positive effects on the lipid ratios in general, only except the TG/HDL-C ratio in females. Noticeably, the decreased apoB100/apoAI ratio was associated with the A allele of hepatic lipase G-250A polymorphism only in males. |
| Shatwan IM et al., 2016 [89] | Analysis of the influence of two commonly studied LPL polymorphisms (rs320, HindIII; rs328, S447X) on postprandial lipaemia, in 261 participants using a standard sequential meal challenge. | Novel finding on the effect of the LPL S447X polymorphism on the postprandial glucose and gender-specific impact of the polymorphism on fasting and postprandial TAG concentrations in response to sequential meal challenge in healthy participants. The sex-specific results were only detected in men. |
| Jacobo-Albavera L et al., 2015 [90] | Analysis of whether gender, menopausal status and macronutrient proportions of diet modulate the effect of the (ABCA1) R230C variant on various metabolic parameters. | First study reporting a gender-specific interaction between ABCA1/R230C variant and dietary carbohydrate and fat percentages affecting Visceral adipose tissue (VAT) / subcutaneous adipose tissue (SAT) ratio, gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), adiponectin levels and HOMA index. This study confirmed a previously reported gender-specific ABCA1-diet interaction affecting HDL-C levels. |
| Zhang Z et al., 2011 [91] | Investigation of the association between the sterol regulatory element-binding protein-1c gene (SREBP-1c) rs2297508 and the changes in lipid profiles in a high-carbohydrate and low-fat diet in a Chinese population. | The C allele of the rs2297508 polymorphism was associated with a retardation of the increases in serum triacylglycerol, serum insulin, and HOMA-IR in females and with the elevated serum HDL-C in males after the high-carbohydrate/low fat (high-CHO/LF) diet. |
| Barragán R et al., 2018 [92] | Analyzed the age influence on the intensity rating of the five basic tastes: sweet, salty, bitter, sour and umami (separately and jointly in a "total taste score") and their modulation by sex and genetics in a relatively healthy population. | Women perceived taste significantly more intense than men (p = 1.4 × 10−8 for total taste score). Significant associations were, found between a higher perception of sour taste and a higher preference for it in women. In contrast, the higher perception of sweet was significantly associated with a higher preference for bitter in both, men and women. The TAS2R38-rs713598 SNP had a significant interaction with sex. |
| Lauritzen L et al., 2017 [93] | Mendelian randomization study to explore whether SNPs in fatty acid desaturase (FADS) and elongase (ELOVL) genes were associated with school performance in a sex-specific manner. | Associations between rs1535 minor allele homozygosity and rs174448 major allele carriage and improved performance in boys but not in girls was found, thereby counteracting existing sex differences. |
| Obregón AM et al., 2017 [94] | Analysis of the association between the DRD2 rs1800497 polymorphism and eating behavior in Chilean children. | In the sex-specific analysis, the TaqI A1 allele was associated with higher scores on Satiety Responsiveness and Emotional Undereating subscales in obese girls, and higher scores of Enjoyment of Food subscale in boys. |
| Roumans NJ et al., 2015 [95] | Investigation of whether genetic variation in extracellular matrix (ECM) -related genes is associated with weight regain among participants of the European DiOGenes study. | Variants of ECM genes were associated with weight regain after weight loss in a sex-specific manner. |
| Ericson U et al., 2013 [96] | Interaction analysis between IRS1 rs2943641 and macronutrient intakes on incident T2D and percentage body fat in the Malmö Diet and Cancer cohort. | The IRS1 rs2943641 interacted with carbohydrate and fat intakes on incident T2D in a sex-specific manner. A protective association between the rs2943641 T allele and T2D was restricted to women with low carbohydrate intake and to men with low fat intake. |
| Dedoussis GV et al., 2011 [97] | Investigation of the age-related association between the Pro12Ala variant (rs1801282) and diet in obesity-related traits in children. | Adiposity in children was influenced by the Pro12Ala polymorphism in a sex-specific and age-dependent manner. |
| Nettleton JA et al., 2009 [98] | Analysis of whether dietary macronutrient intake modified associations between ANGPTL4[E40K] variation and TG and HDL-C in White men and women from the Atherosclerosis Risk in Communities study. | In men, but not women, the inverse association between carbohydrate and HDL-C was stronger in A allele carriers (beta+/-S.E. -1.80+/-0.54) than non-carriers (beta+/-S.E. -0.54+/-0.11, p(interaction) = 0.04 in men and 0.69 in women; p 3-way interaction = 0.14). |
| Gastaldi M et al., 2007 [99] | Analysis of the effect of fatty acid binding protein 2 (FABP2) Ala54Thr and microsomal triacylglycerol transfer protein (MTTP) -493G/T variations on plasma lipid markers, at baseline and on the response to the 3-mo Medi-RIVAGE study. | These 2 polymorphic loci are thus differently associated with the baseline lipid markers as well as with the response to nutritional recommendations, but both presented a marked sex-specific profile, with the response to diet being particularly efficient in men homozygous for the MTTP -493T allele. |
| Alkhalaf A et al., 2015 [100] | This study investigated whether 5L-5L in the CNDP1 gene was associated with mortality and progression of renal function loss and to what extent this effect was modified by sex. | The association between CNDP1 and cardiovascular mortality was sex-specific, with a higher risk in women with 5L-5L genotype. CNDP1 was not associated with all-cause mortality or change in epidermal growth factor receptor (EGFR). |
| van Dijk SJ et al., 2016 [101] | A double-blind randomized placebo-controlled trial in pregnant women to test whether a defined nutritional exposure in utero, docosahexaenoic acid (DHA), could alter the infant epigenome. | Maternal DHA supplementation during the second half of pregnancy had small effects on DNA methylation of infants. However, the number of differential methylated loci (DMRs) at birth was greater in males (127 DMRs) than in females (72 DMRs) separately, indicating a gender-specific effect. |
| Gonzalez-Nahm S et al., 2017 [102] | Association between maternal adherence to a Mediterranean diet pattern during pregnancy and infant DNA methylation at birth. | There was an association between overall diet pattern and methylation at the 9 DMRs analyzed and suggests that maternal diet can have a sex-specific impact on infant DNA methylation at specific imprinted DMRs. |
| Borgo F et al., 2018 [103] | Comparison of the gut microbiota is in at least two separate microbial populations, the lumen-associated (LAM) and the mucosa-associated microbiota (MAM). Next generation sequencing was used). | LAM and MAM communities seemed to be influenced by different host factors, such as diet and sex. Female MAM was enriched in Actinobacteria (with an increased trend of the genus Bifidobacterium), and a significant depletion in Veillonellaceae. |
| Bolnick DI et al., 2014 [104] | Analysis of the factors related to the composition of gut microbiota, mainly the host genotyping. | The results indicated that microbiota composition depends on interactions between host diet and sex within populations of wild and laboratory fish, laboratory mice and humans. The diet-microbiota associations were sex dependent. Further experimental work confirmed that microbiota was different males versus females and suggested that therapies to treat dysbiosis might have sex-specific effects |