Genetic variants on apolipoprotein gene cluster influence triglycerides with a risk of coronary artery disease among Indians.
Apolipoprotein C3 and apolipoprotien A5 are proteins coded from the APOA1/C3/A4/A5 gene cluster. Sst I polymorphism on apolipoprotein C3 and -1131C polymorphism of apolipoprotien A5 are key variants involved in triglyceride metabolism and cause a significant cardio-metabolic risk. Here, we have evaluated these two variants for their roles in coronary artery disease in patients of the Indian population. The apolipoprotein gene cluster variants were analysed in 416 angiographically determined coronary artery disease patients and matched 416 controls using polymerase chain reaction-restriction fragment length polymorphism. The characteristics of the study subjects were analyzed statistically for their association with the polymorphisms. The alleles were combined as haplotypes and their combined risks were evaluated. The minor allele genotypes of both apolipoprotein C3 (S2) and apolipoprotien A5 (C) had a significant risk for coronary artery disease. The S2 allele genotyped patients had a significantly increased triglyceride level (P < 0.001) and increased triglycerides were observed among both patient and control CC genotype carriers. We identified the haplotype S2/C with a significant increased risk (P < 0.001) to coronary artery disease with increased levels of circulating triglycerides compared to other haplotypes in patients. We conclude that the variants on apolipoprotein C3 and apolipoprotien A5 modulate serum triglyceride levels and increase the risk of coronary artery disease.
AshokKumar
Manickaraj
M
International Centre for Cardiothoracic and Vascular Diseases, Frontier Lifeline, Chennai, India.
Subhashini
Navaneethan Gnana Veera
NG
SaiBabu
Ramineni
R
Ramesh
Arabandi
A
Cherian
Kotturathu Mammen
KM
Emmanuel
Cyril
C
D001053:Apolipoproteins / Q000235:genetics*; D001786:Blood Glucose / Q000235:genetics; D016022:Case-Control Studies; D016001:Confidence Intervals; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014280:Triglycerides / Q000097:blood*
D001053:Apolipoproteins; D001786:Blood Glucose; D014280:Triglycerides
BMC Med Genet. 2006 Oct 10;7:76
17032446
Indian J Clin Biochem. 2003 Jul;18(2):34-8
23105390
Acta Cardiol. 1995;50(3):227-40
7676762
Lipids Health Dis. 2008 Sep 19;7:33
18801202
BMC Genet. 2002 Jun 06;3:9
12052247
J Am Coll Cardiol. 2001 Sep;38(3):682-7
11527617
Mol Genet Metab. 2004 Nov;83(3):280-6
15542401
Nature. 2000 Sep 14;407(6801):233-41
11001066
Circulation. 2004 Sep 28;110(13):1868-73
15451808
Biochem Genet. 1993 Aug;31(7-8):321-8
8274138
Heart. 2008 Jan;94(1):16-26
18083949
Atherosclerosis. 2009 Sep;206(1):148-52
19344899
Biochim Biophys Acta. 2008 Jul-Aug;1782(7-8):447-52
18395529
Curr Opin Lipidol. 2005 Apr;16(2):153-66
15767855
Science. 2001 Oct 5;294(5540):169-73
11588264
Atherosclerosis. 1991 Apr;87(2-3):239-47
1906714
JAMA. 2007 Jan 17;297(3):286-94
17227980
Hum Mol Genet. 2002 Nov 15;11(24):3039-46
12417525
Annu Rev Genomics Hum Genet. 2004;5:189-218
15485348
Clin Chem Lab Med. 2008;46(12):1714-9
19055447
Clin Chem. 2002 Sep;48(9):1597-600
12194944
J Lipid Res. 2003 Jun;44(6):1167-73
12671030
Am J Clin Nutr. 2008 Jun;87(6):1932-8
18541587
Curr Opin Lipidol. 1997 Jun;8(3):154-8
9211063
J Lipid Res. 2004 Apr;45(4):750-6
14729863
Lancet. 2004 Sep 11-17;364(9438):937-52
15364185