Genotype-based precision nutrition strategies for the prediction and clinical management of type 2 diabetes mellitus

Table 1 Gene-diet interactions concerning the risk of developing type 2 diabetes mellitus and individual responses to nutritional interventions

SNP reference	Gene symbol	Gene function	Risk allele	Dietary interaction	Main outcome	Population	Ref.
rs7903146	TCF7L2	Wnt signaling pathway	T	High dessert and milk intakes (above median)	Higher T2DM risk	Algerian	[83]
rs7903146	TCF7L2	Wnt signaling pathway	C	Fiber intake	Inversely associated with T2DM incidence	Swedish	[84]
rs7903146 and rs4506565	TCF7L2	Wnt signaling pathway	rs7903146 (C) and rs4506565 (A)	Per daily 30-g increased intake of whole grain and per daily 5-g increased intake of cereal fiber	Decreased risk of developing T2DM	Swedish men	[85]
rs7901695	TCF7L2	Wnt signaling pathway	T	Upper protein intake quantiles	Higher HbA1c, HOMA-IR, blood glucose, and insulin levels	Polish	[86]
rs6696797, rs4244372, and rs10881197	AMY1	Carbohydrate digestion	rs6696797 (A), rs4244372 (A), rs10881197 (G)	Carbohydrate intake > 65% of total energy	Higher T2DM incidence	Korean women	[87]
rs2233998	TAS2R4	Bitter taste perception	T	High intakes of carbohydrates or sugars (highest tertile) and low intakes of fruits or vegetables (lowest tertile)	Higher T2DM incidence	Korean women	[88]
rs1801282 and rs3856806	PPARG	Fatty acid storage and glucose metabolism	rs1801282 (Pro12), rs3856806 (C)	High fat consumption (the third sex-specific tertile of fat intake	Increased T2DM risk	French	[89]
rs7756992	CDKAL1	Beta cells function	G	First tertiles of protein and fat intakes	Higher T2DM risk	Korean	[90]
rs7754840	CDKAL1	Pancreatic beta cells function	G	Habitual coffee intake	Lower risk of prediabetes and T2DM	East Asians	[91]
rs5215	KCNJ11	Formation of ATP-sensitive potassium (K-ATP) channels in pancreatic beta cells	C	Habitual coffee intake	Lower risk of prediabetes and T2DM	East Asians	[91]
rs4402960	IGF2BP2	Cellular metabolism modulation by post transcriptional regulation	T	Habitual coffee intake	Lower risk of prediabetes and T2DM	East Asians	[91]
rs10517030	PGC-1α	Regulation of genes involved in energy metabolism	C	Low-energy diet (daily consumption less than estimated energy intake)	Positively associated with T2DM prevalence and insulin resistance and negatively associated with beta cell function	Koreans	[92]
rs6265	BDNF	Survival and growth of neurons, and synaptic efficiency and plasticity	Met	Low-energy (daily consumption less than estimated daily energy intake), low-protein (< 13% daily energy), and high-carbohydrate (70% daily energy)	Lower risk for T2DM	Koreans	[93]
rs161364 and rs8065080	TRPV1	Receptor for capsaicin, non-selective cation channel, and participates in transduction of painful thermal stimuli	rs161364 (T) and rs8065080 (C)	High preference for oily foods and high fat intake from oily foods	Lower risk for T2DM	Koreans	[94]
rs77768175, rs2074356 and rs11066280	HECTD4	Glucose homeostasis and glucose metabolic process	rs77768175 (A), rs2074356 (G), rs11066280 (T)	Alcohol consumption (> 5 g/d)	Significantly increased risks of T2DM	East Asians	[95]
rs10830963	MTNR1B	Regulation of the circadian actions of melatonin	G	Increasing dietary iron intake	Increased risk of elevated fasting glucose, higher fasting glucose, and higher HbA1c	Chinese	[96]
rs10830963	MTNR1B	Regulation of the circadian actions of melatonin	G	Late dinner	Impaired glucose tolerance	European	[97]
rs10830963	MTNR1B	Regulation of the circadian actions of melatonin	G	Late eating	Impaired glucose tolerance and insulin secretion defects	European	[98]
rs2943641	IRS1	Insulin signaling	T	Lower tertiles of carbohydrate intake (women) and lowest tertile of fat intake (men)	Decreased risk of T2DM	Swedish	[99]
rs7578326 and rs2943641	IRS1	Insulin signaling	rs7578326 (G) and rs2943641 (T)	Low SFA-to-carbohydrate ratio (≤ 0.24)	Lower risk of insulin resistance and metabolic syndrome	American	[100]
rs10423928	GIPR	Insulin release stimulation	T	Highest carbohydrate quintile	Decreased T2DM risk	Swedish	[101]
rs3014866	S100A9	Cell cycle progression and differentiation	C	High dietary SFA: Carbohydrate ratio intake	Higher insulin resistance	Spanish white adults, North American non-Hispanic white adults, and Hispanic adults	[102]
rs709592	PSMD3	Maintenance of protein homeostasis	T	Low carbohydrate intake (≤ 49.1% energy)	Higher insulin resistance	Americans	[103]
rs8065443	PSMD3	Maintenance of protein homeostasis	A	Low (n-3):(n-6) PUFA ratio (≤ 0.11)	Higher insulin resistance	Americans	[103]
rs7645550	KCNMB3	Control of smooth muscle tone and neuronal excitability	T	Low (n-3):(n-6) PUFA ratio (≤ 0.11)	Lower insulin resistance	Americans	[104]
rs1183319	KCNMB3	Control of smooth muscle tone and neuronal excitability	G	High (n-3):(n-6) PUFA ratio (> 0.09)	Higher HbA1c levels	Hispanics	[104]
rs2270188	CAV2	Signal transduction, lipid metabolism, cellular growth control and apoptosis	T	Increase of daily fat intake from 30% to 40% energy	Greater risk of T2DM	European	[105]
rs10923931	NOTCH2	Wnt signaling pathway	T	Increasing fiber intake	Lower T2DM risk	Swedish	[106]
rs4457053	ZBED3	Wnt signaling pathway	G	Increasing fiber intake	Lower T2DM risk	Swedish	[106]
rs3765467	GLP1R	Insulinotropic action of GLP-1 in β-cells	G	Highest tertiles of energy, protein and carbohydrate consumption	Higher risk for decreased insulin secretion	Japanese men	[107]
rs9939609	FTO	Regulation of energy intake	A	Low adherence to the Mediterranean diet (≤ 9 points)	Higher risk of prevalent T2DM	Spanish	[108]
rs9939609	FTO	Regulation of energy intake	A	Low folate intake (< 406 μg/d)	Higher fasting plasma glucose concentrations	Spanish	[108]
rs17782313	MC4R	Hypothalamic leptin-melanocortin signaling pathway	C	Low adherence to the Mediterranean diet (≤ 9 points)	Higher risk of prevalent T2DM	Spanish	[108]

SNP: Single nucleotide polymorphism; T2DM: Type 2 diabetes mellitus; SFA: Saturated fatty acids; PUFA: Polyunsaturated fatty acids; HbA1c: Glycosylated hemoglobin; HOMA-IR: Homeostasis model assessment-estimated insulin resistance; GLP-1: Glucagon-like peptide-1; TCF7L2: Transcription factor 7 like 2; AMY1: Amylase 1; PPARG: Peroxisome proliferator-activated receptor gamma; IGF2BP2: Insulin-like growth factor 2 binding protein 2; PGC-1α: Proliferator-activated receptor-gamma coactivator-1alpha; BDNF: Brain-derived neurotrophic factor; TRPV1: Transient receptor potential vanilloid-1 channel; HECTD4: HECT domain E3 ubiquitin protein ligase 4; MTNR1B: Melatonin receptor 1B; IRS1: Insulin receptor substrate-1; GIPR: Glucose-dependent insulinotropic polypeptide receptor; CAV2: Caveolin-2; ZBED3: Zinc finger BED-type containing 3; FTO: Fat mass and obesity associated; MC4R: Melanocortin 4 receptor.