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== Clinical significance ==
In humans, plasma triglycerides such as triacylglycerols have been long debated as an important risk factor for not only cardiovascular disease<ref>{{Cite journal|last=Miller|first=Michael|last2=Stone|first2=Neil J.|last3=Ballantyne|first3=Christie|last4=Bittner|first4=Vera|last5=Criqui|first5=Michael H.|last6=Ginsberg|first6=Henry N.|last7=Goldberg|first7=Anne Carol|last8=Howard|first8=William James|last9=Jacobson|first9=Marc S.|date=2011-05-24|title=Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association|url=https://www.ncbi.nlm.nih.gov/pubmed/21502576|journal=Circulation|volume=123|issue=20|pages=2292–2333|doi=10.1161/CIR.0b013e3182160726|issn=1524-4539|pmid=21502576}}</ref> but also for other relevant morbidities, such as cancer, renal disease, suicide, and all-cause mortality.<ref>{{Cite journal|last=Hubacek|first=Jaroslav A.|date=2016-10-30|title=Apolipoprotein A5 fifteen years anniversary: Lessons from genetic epidemiology|url=https://www.ncbi.nlm.nih.gov/pubmed/27496343|journal=Gene|volume=592|issue=1|pages=193–199|doi=10.1016/j.gene.2016.07.070|issn=1879-0038|pmid=27496343}}</ref> The APOA5 gene was found by comparative sequencing of ~200 kbp of human and mice DNA as the last member of the gene cluster of apolipoproteins located on human chromosome 11 at 11q23. Two mouse transgenic mouse models (APOA5 transgenic and APOA5 knockout) confirmed the important role of this gene in plasma triglyceride levels of plasma triglycerides. Obesity and metabolic syndrome are both closely related to plasma triglyceride levels and APOA5. Recent meta-analyses suggest that the effect on metabolic syndrome development is more profound for rs662799 in Asian population and for rs3135506 for Europeans.<ref>{{Cite journal|last=Xu|first=Chunxiao|last2=Bai|first2=Rongpan|last3=Zhang|first3=Dandan|last4=Li|first4=Zhenli|last5=Zhu|first5=Honghong|last6=Lai|first6=Maode|last7=Zhu|first7=Yimin|date=2013-01-01|title=Effects of APOA5 -1131T>C (rs662799) on fasting plasma lipids and risk of metabolic syndrome: evidence from a case-control study in China and a meta-analysis|url=https://www.ncbi.nlm.nih.gov/pubmed/23468858|journal=PloS One|volume=8|issue=2|pages=e56216|doi=10.1371/journal.pone.0056216|issn=1932-6203|pmid=23468858}}</ref><ref>{{Cite journal|last=Liu|first=Cun-Fei|last2=Yang|first2=Qun-Fang|last3=Chen|first3=Xing-Lin|last4=Liu|first4=Cheng-Yun|date=2012-10-01|title=Apolipoprotein a5 gene polymorphism and risk for metabolic syndrome: a meta-analysis|url=https://www.ncbi.nlm.nih.gov/pubmed/22905904|journal=Genetic Testing and Molecular Biomarkers|volume=16|issue=10|pages=1241–1245|doi=10.1089/gtmb.2012.0183|issn=1945-0257|pmid=22905904}}</ref><ref>{{Cite journal|last=Jiang|first=Chao Qiang|last2=Liu|first2=Bin|last3=Cheung|first3=Bernard M. Y.|last4=Lam|first4=Tai Hing|last5=Lin|first5=Jie Ming|last6=Li Jin|first6=Ya|last7=Yue|first7=Xiao Jun|last8=Ong|first8=Kwok Leung|last9=Tam|first9=Sidney|date=2010-11-01|title=A single nucleotide polymorphism in APOA5 determines triglyceride levels in Hong Kong and Guangzhou Chinese|url=https://www.ncbi.nlm.nih.gov/pubmed/20571505|journal=European journal of human genetics: EJHG|volume=18|issue=11|pages=1255–1260|doi=10.1038/ejhg.2010.93|issn=1476-5438|pmid=20571505}}</ref> Moreover, meta-analysis that focused on rs662799 and the risk of type 2 diabetes mellitus has suggested a significant association in Asian populations, but not in European populations.<ref>{{Cite journal|last=Lee|first=Ki Ho|last2=Kim|first2=Oh Yoen|last3=Lim|first3=Hyo Hee|last4=Lee|first4=Young Jin|last5=Jang|first5=Yangsoo|last6=Lee|first6=Jong Ho|date=2010-11-01|title=Contribution of APOA5-1131C allele to the increased susceptibility of diabetes mellitus in association with higher triglyceride in Korean women|url=https://www.ncbi.nlm.nih.gov/pubmed/20303129|journal=Metabolism: Clinical and Experimental|volume=59|issue=11|pages=1583–1590|doi=10.1016/j.metabol.2010.02.008|issn=1532-8600|pmid=20303129}}</ref><ref>{{Cite journal|last=Yin|first=Yan-Wei|last2=Sun|first2=Qian-Qian|last3=Wang|first3=Pei-Jian|last4=Qiao|first4=Li|last5=Hu|first5=Ai-Min|last6=Liu|first6=Hong-Li|last7=Wang|first7=Qi|last8=Hou|first8=Zhi-Zhen|date=2014-01-01|title=Genetic polymorphism of apolipoprotein A5 gene and susceptibility to type 2 diabetes mellitus: a meta-analysis of 15,137 subjects|url=https://www.ncbi.nlm.nih.gov/pubmed/24586566|journal=PloS One|volume=9|issue=2|pages=e89167|doi=10.1371/journal.pone.0089167|issn=1932-6203|pmid=24586566}}</ref>
=== As a risk factor ===
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A large meta-analysis of 101 studies<ref name = "TCDGC_2001"/> confirmed a risk associated with the presence of the minor APOA5 allele -1131C and coronary heart disease. The odds ratio was 1.18 for every C allele. There are far fewer studies on the second common APOA5 polymorphism, Ser19>Trp, even though available studies have detected that its effect on plasma triglycerides is similar to C-1131>T. Nevertheless, the minor Trp allele is also associated with increased risk of CVD, and it seems that especially homozygotes and carriers of more minor alleles (both -1131C and 19Trp) are at higher risk of CVD.<ref name = "Hubacek_2004">{{cite journal | vauthors = Hubacek JA, Skodová Z, Adámková V, Lánská V, Poledne R | title = The influence of APOAV polymorphisms (T-1131>C and S19>W) on plasma triglyceride levels and risk of myocardial infarction | journal = Clinical Genetics | volume = 65 | issue = 2 | pages = 126–30 | date = Feb 2004 | pmid = 14984471 | doi=10.1111/j.0009-9163.2004.00199.x}}</ref>
=== Clinical Marker ===
A multi-locus genetic risk score study based on a combination of 27 loci, including the APOA5 gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).<ref>{{Cite journal|last=Mega|first=Jessica L.|last2=Stitziel|first2=Nathan O.|last3=Smith|first3=J. Gustav|last4=Chasman|first4=Daniel I.|last5=Caulfield|first5=Mark J.|last6=Devlin|first6=James J.|last7=Nordio|first7=Francesco|last8=Hyde|first8=Craig L.|last9=Cannon|first9=Christopher P.|date=2015-06-06|title=Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials|url=https://www.ncbi.nlm.nih.gov/pubmed/25748612|journal=Lancet (London, England)|volume=385|issue=9984|pages=2264–2271|doi=10.1016/S0140-6736(14)61730-X|issn=1474-547X|pmid=25748612}}</ref>
=== BMI, metabolic syndrome ===
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