A study of the role of GATA2 gene polymorphism in coronary artery disease risk traits.
The GATA2 is a multi-catalytic transcription factor believed to play an important role in regulating inflammatory processes, largely contributory to cardiovascular-related events. However, its role in coronary artery disease (CAD) risk traits remains poorly understood. In a preliminary study using Affymetrix 250K, we established a link on chromosome (chr) 3, which harbors the GATA2 gene, to early onset of CAD in two families with heterozygous familial hyperlipidemia (HFH), suggesting a role for the gene in metabolic-related CAD in the general population. We then sequenced the gene in the families and an additional 200 individuals in the general population, followed by an association study for 8 SNPs on CAD metabolic risk traits in a total of 4557 individuals (2386 CAD cases versus 2171 angiographed controls) by the Applied Biosystems real-time PCR system. The rs1573949_C [1.15(1.00-1.32); p=0.049] was associated with MI, rs7431368_AA [5.2(1.05-26.60); p=0.43] conferred risk for harboring low high density lipoprotein, and obesity was linked to rs10934857_AA [5.69(1.04-30.98); p=0.045] following Bonferroni corrections and multivariate adjustments for confounders. Furthermore, a haplotype CCCGGGTC (χ(2)=4.23; p=0.04) constructed from the eight studied SNPs and its 6-mer derivative CGGGTC (χ(2)=5.05; p=0.025) were associated with CAD. Obesity was associated with the 6-mer CATAAA (χ(2)=3.66; p=0.049), and hypercholesterolemia was linked to the 8-mer CCTGGACC (χ(2)=6.02; p=0.014), but most significantly so with its 5-mer derivative, CTGGA (χ(2)=6.75; p=0.009). On the other hand, high low density lipoprotein was linked to TGG (χ(2)=4.48; p=0.034). Our study points to an association of GATA2 at both SNP and haplotype levels with important metabolic risk traits for atherosclerosis.
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Nzioka P
NP
Muiya
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Salma
S
Wakil
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Mohammed
M
Al-Najai
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Asma I
AI
Tahir
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Batoul
B
Baz
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Editha
E
Andres
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Olyan
O
Al-Boudari
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Nada
N
Al-Tassan
King Faisal Heart Institute, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Maie
M
Al-Shahid
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia.
Brian F
BF
Meyer
Genetics Department, King Faisal Specialist Hospital and Research Centre, P. O. Box 3354, Riyadh 11211, Saudi Arabia. Electronic address: dzimiri@kfshrc.edu.sa.
Nduna
N
Dzimiri
D050197:Atherosclerosis / Q000235:genetics*; D001483:Base Sequence; D003324:Coronary Artery Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D050171:Dyslipidemias / Q000235:genetics; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics; D006973:Hypertension / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012307:Risk Factors; D017422:Sequence Analysis, DNA
D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human
Coronary artery disease; GATA2 polymorphism; Haplotypes; Hyperlipidemia; Obesity