Ever wonder why a certain medication may work great for a friend and do nothing for you? Interestingly, it could involve specific genes that transport the medication into and out of your cells.
Let’s take fexofenadine (Allegra) for example. You have watery eyes and a drippy nose during spring allergy season and take some Allegra to help with the symptoms. Once swallowed, that medication dissolves, goes through absorption, and then transports to the cells where it acts. Plus, it must stay inside of those target cells.
How the medication stays inside the cells – instead of being transported right back out of the cell – plays into genetics.
Certain medications and toxins are transported back out of cells by an ATP-binding cassette transporter protein encoded by the ABCB1 gene.
In the epithelial cells lining your intestines, the ABCB1 proteins involve the pumping of substances back into the intestinal lumen. So imagine taking an Allegra; it then dissolves, gets absorbed, and then part of that gets pumped back into the intestines to be eliminated.
Genetic variants in ABCB1 affect the amount staying in the cells vs the elimination. (through intestines, bile, urine). In general, it is a good thing for the body to get rid of a substance that it thinks might be toxic.
While an allergy medication not working well for you isn’t really a bid deal, the real problem comes when trying to keep chemotherapy drugs inside of cancer cells. Thus, this gene has been studied in depth for drugs that treat cancer.
ABCB1 gene (multidrug resistance protein, p-glycoprotein):
The genetic variant known as rs1045642 or C3435T has been extensively studied in regards to response to quite a few different drugs. Those who have the AA genotype (23andMe orientation) have less of an efflux (outward flow) of certain drugs — meaning that less of the drug is transported back out of the cell by the ABCB1 transporter.[ref]
Less of a drug transported out of the cell usually indicates higher effectiveness of the drug for that individual. The variant, AA, is fairly common with about 25% of Caucasians carrying it (less frequent in Asian populations).
Check your genetic data for rs1045642 C3435T (23andMe v.4 only)
- AA: reduced drug efflux (less of the drug is moved out of the cell), thus may have a better response to fexofenadine (Allegra), may need lower dosages of some drugs in comparison to those with GG[ref][ref]
- AG: intermediate efflux
- GG: greater efflux (out of the cell) for drugs and toxins, and thus may need higher dosages of some drugs compared to those with AA genotype
Members: Your genotype for rs1045642 is —.
Check your genetic data for rs1128503 C1236T (23andMe v4, v5; AncestryDNA):
- G/G: reduced drug efflux (less of the drug moved out of the cell), thus may have a better response to fexofenadine[ref]
- A/G: intermediate efflux
- A/A: greater efflux out of the cell, may need higher dosages compared with people with the G/G genotype
Members: Your genotype for rs1128503 is —.
Note that the two SNPs above, rs1045642 and rs1128503, are almost always inherited together. In some studies, you may see one or the other rs id referred to.[ref]
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Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.