{"id":3183,"date":"2009-12-24T16:13:01","date_gmt":"2009-12-24T16:13:01","guid":{"rendered":"http:\/\/euvolution.com\/futurist-transhuman-news-blog\/lpa-maybe-theres-something-there-that-wasnt-there-before\/"},"modified":"2009-12-24T16:13:01","modified_gmt":"2009-12-24T16:13:01","slug":"lpa-maybe-theres-something-there-that-wasnt-there-before","status":"publish","type":"post","link":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/genetic-medicine\/lpa-maybe-theres-something-there-that-wasnt-there-before.php","title":{"rendered":"Lp(a) Maybe there’s something there that wasn’t there before?"},"content":{"rendered":"

I unwrapped the NEJM this week and to my surprise it has a <\/span>Lp(a) stuff in it.<\/span><\/a> One of the things we do to prevent heart disease is take family histories. We also check cholesterol levels and include something called a Cardio-CRP. One thing we haven't been including is a Lp(a). Why? The only data I see that is good on this is on women.<\/span><\/p>


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We use validated risk tools like Reynolds and Framingham Risk. It was with great interest that I read about this<\/span> recent \"candidate gene\" model of assessment for Lp(a) genetic link to levels and risk. Clarke et. al.<\/span><\/a><\/div>

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They also looked at the other GWAS linked regions and what they found was most surprising in my mind.<\/span><\/div>

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<\/span>LPA,<\/span><\/i> which encodes<\/span> <\/span><\/sup>apolipoprotein(a), was the only true \"candidate\" gene on this<\/span> <\/span><\/sup>custom array that was significantly associated with coronary<\/span> <\/span><\/sup>disease. <\/span><\/span><\/div>

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Now why would the other regions not be as strongly linked? Or better yet, why was Lp(a) more likely to be linked and associated?<\/span><\/div>

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Well, LPA the gene produces a protein called Lp(a) which is hypothesized to carry oxidized proinflammatory phospholipids, thus promoting inflammation in coronary arteries in turn creating niduses for clot and heart attack.<\/span><\/div>

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What do the other regions do? Dunno. I think that is the teaching point here.<\/span><\/div>

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GWAS great for illuminating possible pathology, which then in turn must be dissected and validated.<\/span><\/div>

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Candidate screens are good for risk markers IFF there is some hint of WTF the proteins are doing for the disease.<\/span><\/div>

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This is why I am just flummoxed by the fact that people are still pushing tests which have little to no clinical use or even prognostic capabilities.<\/span><\/div>

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Listen, you want to discover yourself? Go get a cholesterol, Glycohemoglobin, and complete blood count. Check your blood pressure, check your BMI. If any of these are abnormal, go seek professional help.<\/span><\/div>

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But please, please, please don't use SNPs that have no science behind them as true science or clinical markers. research them, sure. But using them like MDVIP has........Risky guys.<\/span><\/div>

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Which reminds me. <\/span>I am taking care of a patient who recently left MDVIP<\/span><\/a>.......the <\/span>patient had the Navigenics SNP scan done<\/span><\/a>.........what do I find on family history?<\/span><\/div>

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The patient met Bethesda Criteria for HNPCC.........<\/span><\/div>

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Guess someone was too busy scanning Unproven SNPs.<\/span><\/div>

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That being said, this current study by Clarke suggests a few things<\/span><\/div>

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1. Two <\/span>LPA<\/span><\/i> SNPs explain approximately<\/span> <\/span><\/sup>36% of the overall variance in plasma Lp(a) lipoprotein levels. That could be like the CRP story. Yeah CRP levels but no association with risk. Big Whoop, but....<\/span><\/span><\/div>

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2. Both SNPs (one coding for the amino acid substitution<\/span> <\/span><\/sup>I4399M and the other non coding) are associated with coronary<\/span> <\/span><\/sup>disease. Ahem, like to see some replication here......But it could be true.<\/span><\/span><\/div>

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3. After adjustment for the plasma Lp(a) lipoprotein<\/span> <\/span><\/sup>level, the association between <\/span>LPA<\/span><\/i> genotypes and coronary disease<\/span> <\/span><\/sup>was abolished. Well.....that means to me, phenotypic testing with Lp(a) levels may be more useful than I had thought.....And definitely more useful than genotype testing.<\/span><\/span><\/div>

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The Sherpa Says: <\/span><\/b>Hmmmm<\/span><\/b>, maybe we will see much more of this trend. Non-genetic molecular testing being more valuable than genetic testing for risk prediction.....Wait a sec'<\/span><\/b><\/span><\/div>
<\/span> <\/div>
\"\"<\/div>","protected":false},"excerpt":{"rendered":"

I unwrapped the NEJM this week and to my surprise it has a Lp(a) stuff in it. One of the things we do to prevent heart disease is take family histories. We also check cholesterol levels and include something called … Continue reading →<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"limit_modified_date":"","last_modified_date":"","_lmt_disableupdate":"","_lmt_disable":"","footnotes":""},"categories":[5],"tags":[],"class_list":["post-3183","post","type-post","status-publish","format-standard","hentry","category-genetic-medicine"],"modified_by":null,"_links":{"self":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/3183"}],"collection":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/comments?post=3183"}],"version-history":[{"count":0,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/posts\/3183\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/media?parent=3183"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/categories?post=3183"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.euvolution.com\/futurist-transhuman-news-blog\/wp-json\/wp\/v2\/tags?post=3183"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}