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Genetics

Genetics

Gene tests in nutrition:

Your lifestyle controls the function of your genes, not all genes are constantly active. Nutrigenomics involves the study of the effects of nutrition on the function of genes. Genes affect metabolism in a comprehensive way so not every diet affects everybody the same.

Variant APOE4 of the APOE gene:

  • Apolipoprotein E (APOE) is crucial for fat metabolism, particularly for breaking down lipoproteins (including LDL)
  • Types 3/4 and especially 4/4 are associated with high cholesterol levels, carotid artery disease and Alzheimer’s Disease
  • Although the cognitive processes of individuals with the type 4 variant deteriorate faster than usual, their brain function early in life is enhanced, particularly in the hippocampus

Variant Pro 12ALA of the PPARG2 Gene

  • PPARG (Peroxisome Proliferator-activated Receptor Gamma) is a nuclear protein that has an effect on obesity
  • The Ala type is associated with a lowered risk of type 2 diabetes
  • A study on mice found that individuals with this variant, a high fat diet increased obesity more rapidly and thus formed a predisposing factor for diabetes

Variants IVS4G>T and IVS3C>T of the TCF7L2 Gene

  • TCF7L2 is a protein transcription factor
  • These variants are associated with an increased risk of developing type 2 diabetes

Variant TRP64ARG of the B3AR Gene and variant GLN27GLU of the B2AR gene

  • Beta-adrenergic receptors have a significant effect on energy production and the function of the SNS
  • These variants are associated with obesity

Variant RS9939609(A) of the FTO gene

  • FTO = fat mass and obesity-associated protein
  • Individuals with a type A variant have a significantly increased risk of obesity and developing type 2 diabetes

Variant RS4988235 of the MCM6 gene

  • Affects the production of the lactase enzyme (LCT)
  • Individuals with the T type variant usually tolerate lactose
  • The C/T type variant is associated with obesity
  • Individuals with a C/C type variant are likely to be lactose intolerant

Variants HLA-DQ2 and HLA-DQ8 of the HLA-DQ gene

  • HLA-DQ genes encode certain proteins as a part of the immune system
  • These variants are strongly associated with celiac disease

Variant A118G of the OPRM1 gene

  • The OPRM1 gene encodes opioid receptors
  • The type G variant can significantly increase alcohol dependency

Variant 1148M of the PNPLA3 gene

  • This variant of the PNPLA3 gene related to fat metabolism slows the breakdown of triglyceride fats in the liver and thus promotes the onset of fatty liver disease

Variant 164A>C of the CYP1A2 gene

  • Caffeine, mycotoxin, and paracetamol (among others) are broken down in the liver mainly by the CYP1A2 enzyme
  • Each individual’s CYP1A2 enzyme system functions at a different rate
  • Those with a type C variant have a slow enzyme system. Drinking coffee can increase the risk of heart attack and/or blood pressure

Variants C677T and A1298C of the MTHFR gene and variant A66G of the MTRR gene

  • Methylene tetrahydrofolate reductase (MTHFR) is an enzyme needed to convert folic acid and certain other forms of folate into methylfolate (5-MTHF). Folic acid can be found in vitamin supplements and vitamin enriched foods
  • Individuals with these variants are unable to efficiently convert folic acid into active folate. This results in a high homocysteine level, a known risk factor for cardiovascular disease, particularly in individuals with variants C677T and A66G
  • Switching from folic acid to more efficient methylfolate is recommended

Variant A1 (TAQ1A polymorphism) of the ANKK1 gene

  • ANKK1 (ankyrin repeat and kinase domain containing 1) is fundamentally linked to the dopamine D2 receptor (DRD2), i.e. reward and motivation
  • A mutation in this gene is a predisposing factor for addictive behavior (alcohol, tobacco, sugar, gambling, opiates)
  • The A1 allele is especially found in obese (BMI>30) individuals

Variant RS1229984 of the ADH1B gene

  • Accelerates the conversion of alcohol into acetaldehyde (a more rapidly developing hangover)
  • Individuals with this variant have a lowered risk of developing alcoholism

Mutation of the ALDH2 gene in isoenzyme ALDH2-2

  • Significantly lowered isoenzyme ALDH2-2 activity (typically found in North Asia)
  • A predisposing factor for adverse effects from alcohol and alcohol poisoning

The caffeine effects are due to genetic makeup. The CYP1A2 gene affects the body’s ability to remove caffeine from the system, and the VDR gene is associated with caffeine’s negative effects on bone health.

Blood sugar regulation:

  • MC4R: Regulates the function of type 4 melanocortin receptor. The receptor binds an alpha-melanocyte-stimulating hormone (alpha-MSH) which affects the amount of food consumes. The CC genotype of polymorphism rs17782312 of this gene is associated with an increased risk of metabolic syndrome.
  • IRS1: Regulates insulin receptor substrate 1 (IRS1), one of the key proteins to transmit the metabolic signals of insulin. The GA genotype of polymorphism G972R (rs1801278) of the gene is associated with insulin resistance, particularly when a diet high in salt. The GG (rs7578326) and TT (rs2943641) polymorphisms are associated with a lowered risk of insulin resistance, type 2 diabetes, and metabolic syndrome. The risk was significantly lower when the proportion of saturated fat to carbohydrates in the diet was low (<0.25).
  • CRP: Regulates the function of the C-reactive protein which is the key marker of acute inflammation. Used to predict the development of cardiovascular disease. The GG genotype of polymorphism -732A/G of this gene improved the insulin sensitivity triggered by physical exercise.
  • LIPC: Regulates the function of hepatic lipase which hydrolyzes the triglycerides and phospholipids in lipoproteins. It converts IDL molecules into LDL molecules. The TT genotype of polymorphism -514C/T of this gene is associated with increased blood sugar level 2 hours after oral glucose challenge test, as well as increased fasting insulin levels and cholesterol values. However, a negative impact on insulin resistance was not detected. The GG genotype of polymorphism G-250A of this gene is associated with an increased risk of type 2 diabetes.
  • VDR: Regulates the function of vitamin D receptors. The FF genotype of polymorphism Fok1 of this gene is associated with impaired insulin sensitivity and increased risk of type 2 diabetes. This genotype reacts well to taking vitamin D as a dietary supplements, lowering the risk of insulin resistance.
  • ADIPOQ/APM1: Regulates the function of the adiponectin hormone. Involved with the oxidization of fatty acids, glucose metabolism, insulin sensitivity, and the regulation of energy metabolism. The TT (+457>G) and GG (+276G>T) are associated with significantly lowered adiponectin levels and increased insulin resistance. The TG has the strongest link to insulin resistance. In women, the GA and GG is associated with raised adiponectin levels and hyperglycaemia during the 3 year follow up. Increasing the intake of vegetables and walking regularly are effective in lowering adiponectin levels in overweight carriers.

Blood pressure regulation:

  • AGT: Regulates the function of angiotensinogen, a protein produced in the liver that converts renin into angiotensin 1. This is part of the RAA system that regulates blood pressure. The TT(M235T) is associated with high diastolic blood pressure in men but lowered hypertension in women.
  • ATP6AP2: Pro renin receptor gene regulates the function of the renin receptor. Promotes conversion of angiotensinogen into angiotensin 1. Carriers of the C allele (IVS5+169C>T) had lower blood pressure compared to the carriers of the T allele. Also associated with lower levels of aldosterone in circulation.
  • CYP11B2: Regulates function of the aldosterone synthase enzyme, which is involved in the biosynthesis of the hormone aldosterone (salt regulating hormone). The CC (C-344T) is associated with a slightly lowered risk of hypertension compared to the TT.
  • VEGF: Regulates the function of the vascular endothelial growth factors in the blood vessels. Raised levels in blood plasma of those with hypertension. Polymorphisms 634G>C (C allele) and 936C>T (T allele) of this gene are significantly more common in individuals who suffer from hypertension.
  • NOS (1, 2, 3): Regulates nitric oxide synthases. These enzymes catalyze the production of nitric oxide from arginine. The insufficient availability of NO in the inner membrane of blood vessels (endothelium) is a predisposing factor for hypertension. The CC of the NOS1 gene is associated with an increased risk of hypertension and coronary heart disease. The AT of NOS2 is associated with slightly increased risk of hypertension, whereas CC of NOS3 is associated with a significantly increased risk of hypertension.

Memory function:

  • COMT & ANKK1: Regulates the function of the catechol-O-methyltransferase enzyme which breaks down catecholamines such as dopamine in the PFC. Conversely, the DRD2/ANKK1 gene cluster affects density of dopamine receptors in the striatum. Polymorphism rs4680 (Met/Met) of the COMT gene and polymorphism Taq-la (A1+) of the DRD2/ANKK1 gene are associated with improved visual working memory. This is fundamentally linked to the delayed exit of dopamine from the PF area.
  • CACNA1C: Regulates the alpha 1C subunit of the L-type calcium channel (CaV1.2). Calcium channels play a key role in the conversion of electrical activity into biochemical events in nerve cells. Polymorphism rs1006737 of this gene is associated with impaired working memory in healthy individuals, but not those suffering from bipolar disorder.
  • BDNF: Regulates BDNF function, a growth factor for nerve cells specialization and for the survival of existing nerve cells. Memory function, especially in the hippocampus and cortex. The Val/Val genotype of polymorphism rs6265 (Val66Met) of this gene is associated with improved autobiographical memory in elderly individuals that are physically active.
  • OXTR: Regulates the function of the oxytocin receptor. The polymorphism rs237887 of this gene (A/A genotype) is associated with impaired face memory and sociability. Conversely, the G/G genotype is associated with increased sociability and attachment.
  • GRIN2B: Regulates the function of subunit 2 of the NMDA receptor. The NMDA receptor is one of the key neurotransmitter receptors in the brain. Associated with LTP. The CC genotype of polymorphism rs7301328 (C366G) of this gene is associated with impaired verbal memory.
  • ADRA2B: Regulates the function of the alpha-2b adrenergic receptor. The deletion variant of this gene, in which 3 glutamic acids (SNP rs28365031, rs29000568 and rs4066772) are deleted from the receptor-coding gene, is associated with improved emotional memory and the improved ability to notice the negative aspects of a situation.
  • GCR: Regulates the function of the glucocorticoid receptor (GR) in the cells. The stress hormone cortisol and other glucocorticoids bind to the glucocorticoid receptor. The density of these receptors is particularly high in the PFC. The G allele of polymorphism rs6198 (the 9-beta A3669G genotype) of this gene is associated with an improved reaction time in women but not men.

Genetic Tests in Athletic Potential:

ACE: Regulates angiothensin-1-converting enzyme. Affects the regulation of blood pressure, fluid balance, RBC synthesis, tissue oxidation, and the aerobic efficiency of muscles. The ACE I/I is strongly associated with endurance properties whereas the D/D genotype is associated with strength and speed.

ACTN3: Regulates the function of the alpha-actinin-3 protein. This binds fast muscle cells (IIA and IIX) together. The polymorphism rs1815739 of this gene (RR genotype/R577X) is associated with improved speed properties of the muscle cells. Usually present in elite weightlifters and sprinters. Conversely, the XX genotype of the same polymorphism is more often found in endurance athletes, although this association is quite weak. The R577X variant of the ACTN3 gene is the genetic variant most strongly linked to athletic properties.

MCT1: Regulates monocarboxylate transporter 1 protein which has an important function in the transportation of lactate t muscle cells for oxidation. The polymorphism rs1049434 of this gene (AA genotype/A1470T) is associated with fast lactate transportation. Often in endurance athletes. The AA genotype indicates a slower onset of muscle fatigue and faster recovery. TT is more often found in athletes who practice sports in which speed and strength are required.

PPARGC1A: Regulates mitochondrial biogenesis and general function. It works together with the PPAR-gamma nuclear receptor and participates in the regulation of sugar and fat metabolism. Endurance exercise in particular activates the PPARGC1A gene. The polymorphism rs8192678 of this gene (AA genotype/Gly482) is associated with excellent endurance fitness and the improvement of the anaerobic threshold in European men.

ADRB (1, 2, 3): Beta 1, 2, and 3 adrenergic receptors regulate the heart function and adipose tissue metabolism.

  • The ADRB1 gene regulates the function of the beta-1-adrenergic receptor. The polymorphism rs1801252 (CC genotype.49Gly) and haplotype 49Gly:Arg389 of this gene are associated with improved athletic performance.
  • The ADRB2 gene regulates the function of the beta-2-adrenergic receptor. The polymorphisms Gly16Arg and Glu27Gln of this gene are found in athletes. In particular, genotypes Gly16 (GG) and Glu27(GG) and haplotype Gly16:Glu27 are associated with strength athletics and improved strength properties.
  • The ADRB3 gene regulates the function of beta-3-adrenergic receptor. The polymorphism rs4994 of this gene (AC genotype/Trp64Arg) is significantly more often found in top endurance athletes.

COL5A1: Regulates the collagen alpha-1 (V) chain which is associated with flexibility. A link as been found between flexibility and running economy in endurance sports. The polymorphism BstUI RFLP of this gene (rs12722/TT genotype) is associated with good performance in endurance running.

IL-6: Regulates interleukin 6 which acts both as a pro-inflammatory cytokine and an anti-inflammatory myokine (boosts muscle growth). IL-6 is secreted in response to muscle contractions in exercise. The polymorphism rs1800795 of the IL-6 174D/C gene (GG genotype) is associated with positive strength and speed properties in European athletes.

Sleep

  • Melatonin receptors in the pancreas cause insulin production to decrease overnight while maintaining the level of blood sugar. Night-time eating is associated with increased risk of diabetes. Especially those with the GG genotype of the MTNR1B gene.
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