If you want to know if you have the normal copy or a polymorphism of a gene, consider genetic testing but with the caveats mentioned in this book concerning accuracy and privacy. The following genetic variations are reported in 23andMe.com. If you decide that you want to perform genetic testing or you have already gotten your genotype, this section will help you determine what might be helpful next steps.
Companies such as 23andMe.com are limited in the information that they can provide due to sanctions from the FDA, but the reports are inexpensive (about $199 at the time of writing) and provide the raw data. To determine additional results that are easier to interpret, upload your raw data from 23andme.com to Promethease.com or MTHFRSupport.com. These secondary services are inexpensive ways to learn more about traits like disease susceptibility.
Note that sometimes the base-pair letters are transposed depending on the orientation of the gene in the lab you’re using—sometimes genes are read in the forward direction, and sometimes in the reverse direction, depending on the convention of the laboratory.1 For instance, G=C; A=T. GG is equivalent to CC. If your dad is homozygous for the C677T mutation of MTHFR, 23andMe would report it as rs1801133 AA. See more details on reading reports from the 23andMe website.
Gene, Official Name/SNPs, and What to Do
Alzheimer’s and Bad Heart Gene
Official Names/SNPs:
Apolipoprotein E (APOE) is a more complex gene because of multiple variations of two SNPs, rs429358 and rs7412. There are four alleles but one is rare (E1). The most common gene is APOE3/3, in which you inherit the APOE3 allele from each parent (called a genoset or combination of SNPs, gs246). Here are the six common patterns of inheritance.
25% of people have APOE4, which doubles or triples their risk of Alzheimer’s
What to Do: If you have one or two copies of the APOE4 allele (that is, you’re heterozygous or homozygous), follow the instructions in chapter 11. Most important:
• Optimize diet: low-carb, low- or no-grain.
• Fast 12 to 18 hours overnight.
• Sleep 7 to 8.5 hours/day.
• Exercise 30 to 60 minutes a day, 4 to 6 times a week (150 minutes minimum).
• Reduce inflammation (CRP < 1, homocysteine < 7).
• Reduce stress; stimulate brain.
Breast Cancer
Official Names/SNPs:
BRCA1 (at least 122 SNPs)
BRCA2 (at least 129 SNPs)
What to Do: If you have a variant that increases your risk of breast cancer, consider these actions:
• Weight loss if BMI ≥ 25.
• Drink < 3 servings alcohol/week or abstain.
• Get regular breast-cancer screening.
• Possible medication to reduce risk (tamoxifen, raloxifene, aromatase inhibitors).
• Possible prophylactic surgery, if appropriate (removal of breasts and/or ovaries).
Clock
Official Names/SNPs:
Circadian Locomotor Output Cycles Kaput (Clock) / rs1801260
Normal (C;C)
Heterozygous (C;T)
Homozygous (T;T)
What to Do:
• Variants have higher blood ghrelin levels, the hunger hormones, and weight loss resistance.
• Get 8 hours of sleep every night in order to lose weight.
• Keep circadian clock as regular as possible with consistent sleep/wake cycle every day.
Fatso
Official Names/SNPs:
Fat mass and obesity associated (FTO) / rs9939609
Normal (T;T)
Heterozygous (A;T) has 1.3 times the risk for type 2 diabetes and an increased obesity risk
Homozygous (A;A) has 3 times obesity risk and 1.6 times risk for type 2 diabetes
What to Do:
• You are at greater risk of obesity if eating poorly.
• Track fasting glucose and hemoglobin A1c, reduce size of carb portion at meals.
• Exercise and low-carb diet help.
Longevity
Official Names/SNPs: Mechanistic target of rapamycin or mammalian target of rapamycin (mTOR) / multiple SNPs
What to Do:
• Turn off mTOR with intermittent fasting, nutritional ketosis, healthy fats. Additional supplements that help:
– Di-indole methane (DIM)
– N-acetylcysteine
– Resveratrol
– Lipoic acid
Official Names/SNPs: Sirtuin (SIRT1) / multiple SNPs
What to Do:
• Similarly, turn on SIRT1 with intermittent fasting, nutritional ketosis, healthy fats.
• Specifically, increase DHA by eating cold-water fish or take a supplement.
• Tighten blood-sugar control (keep fasting blood sugar 70 to 85 mg/dL, and 2-hour postprandial < 120 mg/dL).
• Bathe in a dry or infrared sauna.
• Exercise regularly, especially burst exercise or adaptive exercise (yoga, Pilates, tai chi).
• Reduce oxidative stress.
Official Names/SNPs:
Forkhead/winged helix box gene, group O3 (FOXO3) / rs2802292 (plus multiple other SNPs)
Normal (T;T)
Heterozygous (G;T) is associated with between 1.5 to 2 times increased likelihood of living to be a centenarian.
Homozygousr (G;G) is associated with between 1.5 to 2.7 times increased likelihood of living to be a centenarian.
What to Do: Sit in a hot, dry sauna for 20 minutes at least four times per week to turn on this gene.
Methylation
Official Names/SNPs:
Methylenetetrahydrofolate reductase (MTHFR) / rs1801133 (there are several)
Normal (G;G)
Heterozygous (A;G) has 35 to 40% reduced MTHFR enzyme activity.
Homozygous (A;A) has 80 to 90% reduced MTHFR enzyme activity.
What to Do: If you have a variant of one or more of these SNPs, you may have an elevated homocysteine level in your blood, and low vitamin B12 and folate. You have a higher probability of poorly processing folic acid. See your functional medicine professional for doses based on your methylation activity and context. Consider supplementing with 5-methylfolate (or L5MTHF), methylcobalamin (vitamin B12), and riboflavin to work around the gene; track homocysteine in the blood.
Vitamin D Receptor
Official Names/SNPs:
VDR / rs1544410
Normal (T;T)
Heterozygous (G;T)
Homozygous (G;G)
What to Do:
• Keep vitamin D 60 to 90 ng/mL for optimal healthspan.