My lower risk for Alzheimer’s may be the silver lining
to being e2/e2 at APOE.
Image courtesy of ImUnicke

When last I left you in my personal genomic journey, I had just discovered that I was e2/e2 at the APOE gene. I was quietly giddy* about this as it meant I was at a lower risk for getting Alzheimer’s. And even more importantly, it meant I didn’t have e4 which would have significantly increased my chances of getting this form of dementia.

Digging a bit deeper I found some more good news. People with e2/e2 usually have lower levels of LDL, the bad cholesterol that increases the risk for a heart attack. This is consistent with my low levels of LDL. Two good effects from one allele!

But there are no free lunches in genetics. For example, having two copies of the delta32 version of the CCR5 gene makes you pretty resistant to HIV infection. But it makes you more susceptible to the West Nile Virus. Having one copy of the sickle cell version of the hemoglobin gene makes you resistant to malaria. But your kids might end up with full blown sickle cell anemia. And so on.

The e2 version of the APOE gene is no different. It makes me less likely to get Alzheimer’s and, most of the time, to have a heart attack. But it means that I can end up with higher triglycerides from what I eat. This is consistent with what I have seen at the doctor’s.

Triglycerides are actually an independent predictor of heart attack risk. So even though my LDL is low, I need to watch my diet to keep the triglycerides down. If I am not careful, my increased triglycerides might cancel out my decreased LDL and so change my reduced heart attack risk to an increased one.

Being e2/e2 also puts me at risk for a relatively rare disease called hyperlipoproteinemia type III (HLP type 3). One reason this disease is rare is because being e2/e2 is rare. For example, only around 0.4% of people of European background have this genetic combination.

But HLP type 3 is obviously more common for me since I am in that 0.4% group already. Still, only 2% of e2/e2 people end up with HLP type 3 so it is a low risk for me. I decided to look into it anyway.

This disease has various symptoms but the most worrisome ones for me are increased risk of heart attack and abnormal glucose tolerance. My fasting glucose levels are stubbornly high whenever I take my yearly blood test. Which makes me wonder if this genetic difference is affecting my glucose tolerance and I am on my way to HLP type 3.

Of course, lots of genetic differences are involved in establishing someone’s glucose tolerance. And the environment plays a role too. So my glucose tolerance might have nothing to do with me starting to get HLP type 3.

Still, I am definitely going to ask my doctor about it at my next visit. It is rare but there are specific blood tests I can ask for that can tell me if I have this condition. Who’d have thought that a lowered risk of Alzheimer’s would only be a silver lining…

*Well, more of a measured giddiness. I know this is just one of the many genes involved in Alzheimer’s but still, it was good news.

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Dr. Barry Starr

Dr. Barry Starr (@geneticsboy) is a Geneticist-in-Residence at The Tech Museum of Innovation in San Jose, CA and runs their Stanford at The Tech program. The program is part of an ongoing collaboration between the Stanford Department of Genetics and The Tech Museum of Innovation. Together these two partners created the Genetics: Technology with a Twist exhibition. You can also see additional posts by Barry at KQED Science, and read his previous contributions to QUEST, a project dedicated to exploring the Science of Sustainability.

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