Polygenic hypercholesterolemia: Examples of GWAS results and their replication in the Czech-Slavonic population

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00023001%3A_____%2F17%3A00060312" target="_blank" >RIV/00023001:_____/17:00060312 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.biomed.cas.cz/physiolres/pdf/66/66_S101.pdf" target="_blank" >http://www.biomed.cas.cz/physiolres/pdf/66/66_S101.pdf</a>

DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Polygenic hypercholesterolemia: Examples of GWAS results and their replication in the Czech-Slavonic population

Popis výsledku v původním jazyce

Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the &quot;gold standard&quot; for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. GWAS confirm the importance of most of the previously identified genes (e.g. APOE, APOB, LDL-R) and recognize the importance of new genetic determinants (e.g. within the CILP2 or SORT1 gene clusters). Nevertheless, the results of GWAS still require confirmation by independent studies, as interethnic and interpopulation variability of SNP effects have been reported. We analyzed an association between eight variants within seven through GWAs detected loci and plasma lipid values in the Czech post-MONICA population sample (N= 2,559). We confirmed an association ( all P &lt; 0.01) between plasma LDL-cholesterol values and variants within the CILP2 (rs16996148), SORT1 (rs646776), APOB (rs693), APOE (rs4420638) and LDL-R (rs6511720) genes in both males ( N= 1,194) and females (N= 1,368). In contrast, variants within the APOB (rs515135), PCSK9 (rs11206510) and HMGCoAR (rs12654264) genes did not significantly affect plasma lipid values in Czech males or females. Unweighted gene score values were linearly associated with LDL-cholesterol values both in males (P&lt; 0.0005) and females (P&lt; 0.00005). We confirmed the effects of some, but not all analyzed SNPs on LDL-cholesterol levels, reinforcing the necessity for replication studies of GWA-detected gene variants.

Název v anglickém jazyce

Polygenic hypercholesterolemia: Examples of GWAS results and their replication in the Czech-Slavonic population

Popis výsledku anglicky

Since 2007, the year of their first widespread use, genome-wide association studies (GWAS) have become the &quot;gold standard&quot; for the detection of causal genes and polymorphisms in all fields of human medicine. Cardiovascular disease (CVD), one of the major causes of morbidity and mortality, is no exception. The first GWAS focused on hypercholesterolemia and dyslipidemia as the major CVD determinants. GWAS confirm the importance of most of the previously identified genes (e.g. APOE, APOB, LDL-R) and recognize the importance of new genetic determinants (e.g. within the CILP2 or SORT1 gene clusters). Nevertheless, the results of GWAS still require confirmation by independent studies, as interethnic and interpopulation variability of SNP effects have been reported. We analyzed an association between eight variants within seven through GWAs detected loci and plasma lipid values in the Czech post-MONICA population sample (N= 2,559). We confirmed an association ( all P &lt; 0.01) between plasma LDL-cholesterol values and variants within the CILP2 (rs16996148), SORT1 (rs646776), APOB (rs693), APOE (rs4420638) and LDL-R (rs6511720) genes in both males ( N= 1,194) and females (N= 1,368). In contrast, variants within the APOB (rs515135), PCSK9 (rs11206510) and HMGCoAR (rs12654264) genes did not significantly affect plasma lipid values in Czech males or females. Unweighted gene score values were linearly associated with LDL-cholesterol values both in males (P&lt; 0.0005) and females (P&lt; 0.00005). We confirmed the effects of some, but not all analyzed SNPs on LDL-cholesterol levels, reinforcing the necessity for replication studies of GWA-detected gene variants.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30201 - Cardiac and Cardiovascular systems

Projekt

<a href="/cs/project/NV15-28277A" target="_blank" >NV15-28277A: Využití genového LDL skóre v diagnostice primárních hypercholesterolemií a odhadu kardiovaskulárního rizika</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Physiological research

ISSN

0862-8408

e-ISSN

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Svazek periodika

66

Číslo periodika v rámci svazku

Suppl.1

Stát vydavatele periodika

CZ - Česká republika

Počet stran výsledku

11

Strana od-do

"S101"-"S111"

Kód UT WoS článku

000398620900012

EID výsledku v databázi Scopus

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