The Insulin signaling protein type 2 gene (INSIG2) is associated with the synthesis of INSIG2 protein which interacts with transcription factors, activating the synthesis of cholesterol and fatty acids.  The variants of the INSIG2 gene have been shown to be associated with body fat accumulation. Specific alleles of this gene are known to either increase or decrease INSIG2 protein levels which are associated with subcutaneous fat accumulation upon exercising.  

Does your 23andme, Ancestry DNA, FTDNA raw data have INSIG2 gene variant information?

CHIP VersionINSIG2 SNPs
23andMe (Use your 23andme raw data to know your INSIG2 Variant)
v1 23andmePresent
v2 23andmePresent
v3 23andmePresent
v4 23andmePresent
V5 23andme (current chip)Present
AncestryDNA  (Use your ancestry DNA raw data to know your INSIG2 Variant)
v1 ancestry DNAPresent
V2 ancestry DNA (current chip)Present
Family Tree DNA  (Use your FTDNA raw data to know your INSIG2 Variant)
OmniExpress microarray chipPresent

Association with Baseline Subcutaneous fat and Obesity:

In the Framingham Heart Study, people with the C variant of the gene were shown to be associated with obesity, measured in terms of BMI. In a recent similar study conducted on a North Indian population, there was a significant association between INSIG2 gene polymorphism and severe obesity. In another study that analyzed the level of subcutaneous fat, women with the C variant of the gene were shown to be associated with higher levels of baseline subcutaneous fat.

Association with Fat Gain/Loss upon Strength Training:

Men with the C variant of the gene were associated with higher gain in subcutaneous fat upon resistance training while men with the G variant showed a loss in subcutaneous fat. In another study, men with the G variant of the allele were shown to be associated with Intramuscular (IMAT) volume in the upper arm after 12 weeks of training than for the subcutaneous fat. In a study on obese children who were on a weight loss program, children with the C variant of the gene were found to lose less weight than children with the G variant.

Association with Hypercholesterolemia: 

In a study conducted on Japanese women, the C variant of the gene was shown to have a protective effect on the progression of hypercholesterolemia when on a high fat diet. On an initial analysis in another study, women with the C variant of the gene showed a lower prevalence for hypercholesterolemia.

GenotypePhenotypeRecommendation
CC[Limitation] More likely to have higher BMI [Limitation] More likely to have higher subcutaneous fat upon resistance training [Advantage] Less likely to have hypercholesterolemia (Women)Likely increase in subcutaneous fat upon strength training Including fitness programs, other than strength training might be more beneficial Additional effort may be required to lose weight when compared to people with the G variant
CGModerate BMI and subcutaneous fat accumulation upon exercisingLikely increase in subcutaneous fat upon strength training Including fitness programs, other than strength training might be more beneficial Additional effort may be required to lose weight when compared to people with the G variant
GG[Advantage] More likely to have lower BMI [Advantage] More likely to have lower subcutaneous fat upon exercising [Limitation] More Likely to have hypercholesterolemia(women)Likely lower subcutaneous fat upon exercising Strength training has not been shown to be associated with increase in subcutaneous fat upon exercising. There is an increase in Intramuscular volume on training, which may benefit bodybuilders

References:

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646703/
  2. https://www.pathway.com/wp-content/uploads/2014/07/Pathway-Fit-MD_Watermarked_rs.pdf
  3. http://www.genesnp.com/
  4. http://www.wellnessgene.com/images/PDF/WellnessGeneSample-Test.pdf
  5. https://www.ncbi.nlm.nih.gov/pubmed/28160769
  6. https://www.ncbi.nlm.nih.gov/pubmed/23941145
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646703/
  8. http://diabetes.diabetesjournals.org/content/57/3/623.long
  9. https://www.ncbi.nlm.nih.gov/pubmed/18570692
  10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958931/

Nutrigenetics, fitness genetics, health genetics are all nascent but rapidly growing areas within human genetics. The information provided herein is based on preliminary scientific studies and it is to be read and understood in that context.”

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