Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F16%3A00467401" target="_blank" >RIV/67985904:_____/16:00467401 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61988987:17110/16:A1601GI3 RIV/00216224:14310/16:00088953

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.jns.2016.01.022" target="_blank" >http://dx.doi.org/10.1016/j.jns.2016.01.022</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.jns.2016.01.022" target="_blank" >10.1016/j.jns.2016.01.022</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index

Popis výsledku v původním jazyce

Dementias of old age, in particular Alzheimer's disease (AD), pose a growing threat to the longevity and quality of life of individuals as well as whole societies world-wide. The risk factors are both genetic and environmental (lifestyle) and there is an overlap with similar factors predisposing to cardiovascular diseases (CVD). Using a case control genetic approach, we have identified a SNP (rs10507391) in ALOX5 gene, previously associated with an increased risk of stroke, as a novel genetic risk factor for AD. ALOX5 gene encodes a 5'-lipoxygenase (5'-LO) activating protein (FLAP), a crucial component of the arachidonic acid/leukotriene inflammatory cascade. A allele of rs4769874 polymorphism increases the risk of AD 1.41-fold (p < 0.0001), while AA genotype. does so 1.79-fold (p < 0.0001). In addition, GG genotype of rs4769874 polymorphism is associated with a modest increase in body mass index (BMI). We discuss potential biochemical mechanisms linking the SNP to AD and suggest possible preventive pharmacotherapies some of which are based on commonly available natural products. Finally, we set the newly identified AD risk factors into a broader context of similar CVD risk factors to generate a more comprehensive picture of interacting genetics and life-style habits potentially leading to the deteriorating mental health in the old age.

Název v anglickém jazyce

Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index

Popis výsledku anglicky

Dementias of old age, in particular Alzheimer's disease (AD), pose a growing threat to the longevity and quality of life of individuals as well as whole societies world-wide. The risk factors are both genetic and environmental (lifestyle) and there is an overlap with similar factors predisposing to cardiovascular diseases (CVD). Using a case control genetic approach, we have identified a SNP (rs10507391) in ALOX5 gene, previously associated with an increased risk of stroke, as a novel genetic risk factor for AD. ALOX5 gene encodes a 5'-lipoxygenase (5'-LO) activating protein (FLAP), a crucial component of the arachidonic acid/leukotriene inflammatory cascade. A allele of rs4769874 polymorphism increases the risk of AD 1.41-fold (p < 0.0001), while AA genotype. does so 1.79-fold (p < 0.0001). In addition, GG genotype of rs4769874 polymorphism is associated with a modest increase in body mass index (BMI). We discuss potential biochemical mechanisms linking the SNP to AD and suggest possible preventive pharmacotherapies some of which are based on commonly available natural products. Finally, we set the newly identified AD risk factors into a broader context of similar CVD risk factors to generate a more comprehensive picture of interacting genetics and life-style habits potentially leading to the deteriorating mental health in the old age.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

—

Projekt

<a href="/cs/project/NT11152" target="_blank" >NT11152: Epidemiologie a genetika Alzheimerovy choroby</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Journal of the Neurological Sciences

ISSN

0022-510X

e-ISSN

—

Svazek periodika

362

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

6

Strana od-do

27-32

Kód UT WoS článku

000372558400005

EID výsledku v databázi Scopus

2-s2.0-84960859031