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Thread: Prediction of cardiovascular risk by genetic variants within the LPA gene region

  1. #1
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    Prediction of cardiovascular risk by genetic variants within the LPA gene region

    Prediction of cardiovascular risk by Lp(a) concentrations or genetic variants within the LPA gene region
    Florian Kronenberg
    Abstract
    In the middle of the 1990s the interest in Lp(a) vanished after a few badly performed studies almost erased Lp(a) from the map of biological targets. However, since roughly 10 years the interest has begun to grow again mainly for two reasons: first, genetic studies using easily accessible and high-throughput techniques for genotyping of single-nucleotide polymorphisms (SNPs) have allowed large studies in patients with cardiovascular disease and controls to be performed. This strengthened the earlier findings on a copy number variation in the LPA gene and its association with cardiovascular outcomes. Second, new therapies are on the horizon raising strong and justified hope that in a few years drugs will become available which tremendously lower Lp(a) concentrations. This review article should provide an introduction to the genetic determination of Lp(a) concentrations and considerations whether Lp(a) concentrations or genetic variants are important for the prediction of cardiovascular risk.

    Two variants mentioned in the paper sometimes appear in consumer DNA tests:
    RSID:other>risk
    rs10455872:A>G 23andMe{v5,v4}, AncestryDNA(sometimes)
    rs3798220:T>C 23andMe, AncestryDNA

    Unfortunately I have one copy of the risk allele for rs10455872.

    I have only become aware of this recently and have started diving into the research about Lp(a) in general and rs10455872 in particular.

    If you do have a risk variant, please feel free to contact me by PM or respond to this thread.

    For a vivid graphic of the consequences associated with rs10455872, follow this link to the excellent Finnish site FINNGEN.
    http://r3.finngen.fi/variant/6-160589086-A-G
    Last edited by pmokeefe; 11-17-2020 at 09:21 PM.
    YFull: YF14620 (Dante Labs 2018)

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  3. #2
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    Quote Originally Posted by pmokeefe View Post
    Prediction of cardiovascular risk by Lp(a) concentrations or genetic variants within the LPA gene region
    Florian Kronenberg
    Abstract
    In the middle of the 1990s the interest in Lp(a) vanished after a few badly performed studies almost erased Lp(a) from the map of biological targets. However, since roughly 10 years the interest has begun to grow again mainly for two reasons: first, genetic studies using easily accessible and high-throughput techniques for genotyping of single-nucleotide polymorphisms (SNPs) have allowed large studies in patients with cardiovascular disease and controls to be performed. This strengthened the earlier findings on a copy number variation in the LPA gene and its association with cardiovascular outcomes. Second, new therapies are on the horizon raising strong and justified hope that in a few years drugs will become available which tremendously lower Lp(a) concentrations. This review article should provide an introduction to the genetic determination of Lp(a) concentrations and considerations whether Lp(a) concentrations or genetic variants are important for the prediction of cardiovascular risk.

    Two variants mentioned in the paper sometimes appear in consumer DNA tests:
    RSID:other>risk
    rs10455872:A>G 23andMe
    rs3798220:T>C 23andMe, AncestryDNA

    Unfortunately I have one copy of the risk allele for rs10455872.

    I have only become aware of this recently and have started diving into the research about Lp(a) in general and rs10455872 in particular.

    If you do have a risk variant, please feel free to contact me by PM or respond to this thread.

    For a vivid graphic of the consequences associated with rs10455872, follow this link to the excellent Finnish site FINNGEN.
    http://r3.finngen.fi/variant/6-160589086-A-G
    23andme V2
    rs3798220 T,T
    rs10455872 not available

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    rs10455872: A/A
    rs3798220: T/T

    Phew! That's a relief!

    However, I had a heart attack back in 2014 and have a stent. I also have AFIB, which is just so much fun.

    I was seriously overweight back when I had the heart attack. I consumed a lot of really bad junk - sugar, white flour, loads of other carbs - back then.

    Now I am about one hundred pounds lighter than I was in 2014.

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    Not sure what this means?

    rs10455872 6 161010118 AA

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    Ireland Ireland Connacht Ireland County Roscommon Ireland County Galway Ireland County Mayo
    I am rs10455872 AA and rs3798220 TT.
    All is well. Thankfully, touch wood, I don't know of anyone in my family who has had a heart attack. I always thought that my grandfather could have lived to a great age if he looked after himself. He was obese and didn't have a healthy lifestyle but still lived to 82. He started losing weight but people kept asking if he was sick so he gave up on that. My grandfather's sister is 94, his brother is 91 and another sister is 88. As long as they manage to avoid getting cancer, they seem to live to a great age. Even then, the youngest death was in the 70s so it wasn't too bad.
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    mtDNA Great grandfather: Connella b. c1798 in Co. Roscommon (T2a1a8)
    Y-DNA 2x great grandfather: Higgins b. c1816 in Co. Roscommon (R-DF109)
    Y-DNA 3x great grandfather: Fleming b. c1829 in Co. Roscommon (R-Z23534)

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    Quote Originally Posted by Nqp15hhu View Post
    Not sure what this means?

    rs10455872 6 161010118 AA
    You have two copies of the nonrisk variant for rs10455872. That is good!
    YFull: YF14620 (Dante Labs 2018)

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    interesting now I have to take care of myself much more, I mean physically I consider myself athletic, but in terms of nutrition I usually do not do well. Do you think it doesn't matter? could the factor of exercise and sport win over the hereditary factor and nutrition?

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    Quote Originally Posted by carle4332 View Post
    interesting now I have to take care of myself much more, I mean physically I consider myself athletic, but in terms of nutrition I usually do not do well. Do you think it doesn't matter? could the factor of exercise and sport win over the hereditary factor and nutrition?
    Diet and exercise are important for overall health, of course, but they have not been found to be a factor for Lp(a).

    If you do have one of the risk variants for Lp(a), one way to follow up is to get a blood test.
    The blood test for Lp(a) is not standard, but you may be able to get your your doctor to order it.
    I had a lot of difficulty in getting the test, partly due to the pandemic. But I finally received my tests results a few weeks ago.
    As it turns out, I was relatively lucky, my levels of circulating Lp(a) are higher than normal for the population as a whole, but on the the low end, given my risk variant. So not good, but it could have been much worse.
    Other members of my family who carry the risk variant are still waiting for their blood test results, fingers crossed!

    The treatment options for high Lp(a) are limited at the moment, but there are promising treatments in the pipeline.

    https://www.peoplespharmacy.com/arti...-heart-disease
    YFull: YF14620 (Dante Labs 2018)

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    My 23andme results for rs10455872 - A/G, rs3798220 - T/T. I'm under the Lipid clinic as my Cholesterol and Triglycerides were high, which caused me to have pancreatitis, and then became diabetic after the damage from pancreatitis. They tested me for this quite recently and my Lp(a) was 226nmol. The cholesterol and triglycerides are under control now they've changed me to a different statin. The Lipid clinic thinks I likely inherited it from both sides of the family, my paternal grandfather died after a stroke in his late 40s.
    Ethnogene: 51.4% NW European, 21.6% W European, 10.1% Southeastern African, 9.5% Southeast Asian, 4.4% South Asian, 2% Scandinavian, 1% East African
    Papertrail @ 2xggrandparents: 37.5% London, 25% Dorset, 25% Mauritius, 6.25% Netherlands, 6.25% Hampshire

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    Quote Originally Posted by JFWinstone View Post
    My 23andme results for rs10455872 - A/G, rs3798220 - T/T. I'm under the Lipid clinic as my Cholesterol and Triglycerides were high, which caused me to have pancreatitis, and then became diabetic after the damage from pancreatitis. They tested me for this quite recently and my Lp(a) was 226nmol. The cholesterol and triglycerides are under control now they've changed me to a different statin. The Lipid clinic thinks I likely inherited it from both sides of the family, my paternal grandfather died after a stroke in his late 40s.
    My sympathies.

    My Lipoprotein(a) is 102.9, but even that is still considered high.

    I have another variant rs75692336C>A which is also on the gene LPA and is associated with lower Lp(A) which may be protecting me from some of the bad effects of rs10455872. I inherited my rs75692336 and rs10455872 from different parents.

    Do you happen to know your rs75692336 variants?

    Some of my relatives have our bad variant for rs10455872, but not my good variant for rs75692336, we are still waiting for those Lp(a) results.



    I follow Sam Tsimikas, MD on twitter https://twitter.com/Lpa_Doc
    He regularly posts and his past posts contain a wealth of information on Lp(a) if anyone is interested in digging deeper. His twitter feed is basically an online class for other Lp(a) specialists, so it may be heavy going for nonspecialists.

    rs75692336 and rs6938647 are two good LPA variants that may help protect those of us with the bad variants rs10455872 and rs3798220: Frequent LPA KIV-2 Variants Lower Lipoprotein(a) Concentrations and Protect Against Coronary Artery Disease
    Last edited by pmokeefe; 08-02-2021 at 08:50 PM.
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