ApoE 4/4 linked to 2x risk of severe COVID-19 in UK study

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ApoE 4/4 linked to 2x risk of severe COVID-19 in UK study

Postby NF52 » Tue May 26, 2020 6:47 pm

Mags wrote:https://www.theguardian.com/world/2020/may/26/research-reveals-gene-role-in-both-dementia-and-severe-covid-19
Hi Mags and welcome to the forum! For a new user, you have found a whopper of a study to post! That's why I copied it into a new post with a title that is likely to get some attention.

The "accepted manuscript" of the study can be seen in full by clicking on the PDF link on this page: APOE e4 genotype predicts severe COVID-19 in the UK Biobank community cohort This is an association study using data from about 435,000 European-ancestry UK residents enrolled in a population-based longitudinal study of people. The current median age is 68 (standard deviation +/-8 years). The researchers looked at participants who tested positive for COVID-19 in March- April (most of whom were tested upon hospitalization, so assumed to have severe illness) to see if the 9,022 those with ApoE 4/4 were represented at a higher proportion than the 223, 457 with ApoE 3/3. Here's what they found:
There were 622 positive COVID-19 patients (Table 1)including 37 with e4e4 (positivity rate: 410/100,000) and 401 with e3e3 (179 per 100,000)... The association was similar after removing participants with ApoE e4 associated
diseases that were also linked to COVID-19 severity: participants without dementia (OR2.39, 95% CI: 1.71 to 3.35); hypertension (OR= 2.41, 95% CI: 1.56 to 3.74); coronary artery disease (myocardial infarction or angina) (OR= 2.43, 95% CI: 1.69 to 3.50) or type 2 diabetes OR= 2.51, 95% CI: 1.77 to 3.55)... Including only those known to have been inpatients when tested made little difference to the excess risk associated with ApoE e4e4 status (OR=2.32, 95% CI: 1.54 to 3.29), compared to OR=2.31 (95% CI: 1.65 to 3.24) using all the tested samples...
In conclusion, the ApoE e4e4 allele increases risks of severe COVID-19 infection, independent of pre-existing dementia, cardiovascular disease, and type-2 diabetes. ApoE e4 not only affects lipoprotein function (and subsequent cardio-metabolic diseases) but also moderates macrophage pro-/anti-inflammatory phenotypes [9]. The novel coronavirus SARSCoV-2 causing COVID-19 uses the ACE2 receptor for cell entry. ACE2 is highly expressed in type II alveolar cells in the lungs, where ApoE is one of the highly co-expressed genes[10]. Further investigation is needed to understand the biological mechanisms linking ApoE
genotypes to COVID-19 severity. [Emphasis added.]

BUT: Here's the "don't panic yet" caution in the Guardian article cited by "Mags" from Prof David Curtis, honorary professor at the UCL Genetics Institute, referenced in the article and not an author of the study: [Note: all quotes here are from the Guardian link that Mags provided above.]
He noted that among the study’s limitations, diagnoses of dementia in recent years are unlikely to be captured “I’m afraid this study does not really convince me that the ApoE e4 allele [gene variant] is really an independent risk factor for severe Covid-19 infection,” he said. “I would want to see this tested in a sample where dementia could be more confidently excluded, perhaps a younger cohort. I am sure additional data will soon emerge to illuminate this issue.”

Guess I'll put off that visit to my hair salon.
4/4 and still an optimist!

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Re: ApoE 4/4 linked to 2x risk of severe COVID-19 in UK study

Postby Mags » Tue Jun 02, 2020 1:13 pm

Thank you for this, NF52
4/4 grateful to this community

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