Heterozygous for RAB10 & SAR1A

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cdaniel
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Heterozygous for RAB10 & SAR1A

Post by cdaniel »

I have the APOE 4/4 gene but recently discovered through Nebula that I am also heterozygous for the RAB10 (rs142787485 AG) and SAR1A (rs7653 AG) variants. I can't tell from the study I read if being heterozygous confers any protection or if you need to be homozygous to benefit. Does anyone has any information on these variants? Thanks!

Source on variants: https://genomemedicine.biomedcentral.co ... 017-0486-1
TLS
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Re: Heterozygous for RAB10 & SAR1A

Post by TLS »

According to SNPedia:

Rs142787485: Having a copy of the G "Possibly lower odds (~0.65x) of developing Alzheimer's in individuals at higher risk for the disorder". https://www.snpedia.com/index.php/Rs142787485

Here is the info on the rs7653 SNP:
"A 2017 publication reports that the rs7653(C) allele may be associated with a lower odds of developing Alzheimer's disease in individuals otherwise at higher risk for the disorder. In ~400 individuals from the ADNI cohort tested, the rs7653(C) allele carriers had an odds ratio of 0.35 (p value = 0.0049) compared to non-carriers; however, in ~500 individuals from the CCS cohort subsequently tested, rs7653(C) carriers did not have a statistically significant difference from non-carriers, even though the authors reported that the association was in the "predicted positive direction". This is in contrast to the findings associated with rs142787485, which were significant in both cohorts."
apoe 3/4
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Re: Heterozygous for RAB10 & SAR1A

Post by NF52 »

cdaniel wrote: Tue May 30, 2023 2:18 pm I have the APOE 4/4 gene but recently discovered through Nebula that I am also heterozygous for the RAB10 (rs142787485 AG) and SAR1A (rs7653 AG) variants. I can't tell from the study I read if being heterozygous confers any protection or if you need to be homozygous to benefit. Does anyone has any information on these variants? Thanks!

Source on variants: https://genomemedicine.biomedcentral.co ... 017-0486-1
. You're in luck! Here's what Snpedia has to say about RAB10 (rs142787485 AG)
Possibly lower odds (~0.65x) of developing Alzheimer's in individuals at higher risk for the disorder."
It does not provide a specific risk for SAR1A (rs7653 AG), but does reference both the study you quoted and one with another 400 people that also suggest the "G" variant reduces risk for those at higher risk (i.e. ApoE 4 carriers).
https://www.snpedia.com/index.php/Rs142787485. In the first case, it appears that RAB10 prevents or reduces the formation of amyloid beta, a known risk for Apoe4 carriers based on their percentage of AD cases.

Odds of a negative (reduced) risk of ~0.65x would suggest that the "typical" ApoE 3/4 lifetime risk of 10-20% for Alzheimer's disease based on past diagnoses may be reduced by 2/3 in you to that of of ApoE 3/3, or close enough that healthy lifestyle may be your ticket to longevity. .

Not time to break out the triple bacon cheeseburgers, but definitely worth a happy dance!

Nancy
4/4 and still an optimist!
cdaniel
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Re: Heterozygous for RAB10 & SAR1A

Post by cdaniel »

NF52 wrote: Wed May 31, 2023 6:04 am
cdaniel wrote: Tue May 30, 2023 2:18 pm I have the APOE 4/4 gene but recently discovered through Nebula that I am also heterozygous for the RAB10 (rs142787485 AG) and SAR1A (rs7653 AG) variants. I can't tell from the study I read if being heterozygous confers any protection or if you need to be homozygous to benefit. Does anyone has any information on these variants? Thanks!

Source on variants: https://genomemedicine.biomedcentral.co ... 017-0486-1
. You're in luck! Here's what Snpedia has to say about RAB10 (rs142787485 AG)
Possibly lower odds (~0.65x) of developing Alzheimer's in individuals at higher risk for the disorder."
It does not provide a specific risk for SAR1A (rs7653 AG), but does reference both the study you quoted and one with another 400 people that also suggest the "G" variant reduces risk for those at higher risk (i.e. ApoE 4 carriers).
https://www.snpedia.com/index.php/Rs142787485. In the first case, it appears that RAB10 prevents or reduces the formation of amyloid beta, a known risk for Apoe4 carriers based on their percentage of AD cases.

Odds of a negative (reduced) risk of ~0.65x would suggest that the "typical" ApoE 3/4 lifetime risk of 10-20% for Alzheimer's disease based on past diagnoses may be reduced by 2/3 in you to that of of ApoE 3/3, or close enough that healthy lifestyle may be your ticket to longevity. .

Not time to break out the triple bacon cheeseburgers, but definitely worth a happy dance!

Nancy
Wow, that's incredibly exciting. So, as you read it, as an APOE 4/4 and RAB10 (rs142787485 AG), it could reduce my risk by 2/3 or potentially that of an APOE 3/3 person? I may just get that cheeseburger!
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Re: Heterozygous for RAB10 & SAR1A

Post by NF52 »

cdaniel wrote: Tue May 30, 2023 2:18 pm Wow, that's incredibly exciting. So, as you read it, as an APOE 4/4 and RAB10 (rs142787485 AG), it could reduce my risk by 2/3 or potentially that of an APOE 3/3 person? I may just get that cheeseburger!
Still great news, but have to adjust slightly because I forgot that you (like me) have ApoE 4/4, not 3/4. Currently for people my age (71), it looks the the risk is about 60% (which doesn’t account for lifestyle and other strategies you and I know to use). So a 2/3 reduction would bring that to 20%, which is WAY down to the level of ApoE 3/4. I would take an 80% chance of NOT getting diagnosed with AD any day! Enjoy that “rare” allele!
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cdaniel
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Re: Heterozygous for RAB10 & SAR1A

Post by cdaniel »

NF52 wrote: Wed May 31, 2023 8:34 am
cdaniel wrote: Tue May 30, 2023 2:18 pm Wow, that's incredibly exciting. So, as you read it, as an APOE 4/4 and RAB10 (rs142787485 AG), it could reduce my risk by 2/3 or potentially that of an APOE 3/3 person? I may just get that cheeseburger!
Still great news, but have to adjust slightly because I forgot that you (like me) have ApoE 4/4, not 3/4. Currently for people my age (71), it looks the the risk is about 60% (which doesn’t account for lifestyle and other strategies you and I know to use). So a 2/3 reduction would bring that to 20%, which is WAY down to the level of ApoE 3/4. I would take an 80% chance of NOT getting diagnosed with AD any day! Enjoy that “rare” allele!
That is fantastic. I thought since it was heterozygous and not homozygous, it might not have the same effect. Thank you so much for your reply!
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