A study of the role of GATA2 gene polymorphism in coronary artery disease risk traits

• Published in: Gene Vol. 544; no. 2; pp. 152 - 158
• Main Authors: Muiya, Nzioka P., Wakil, Salma, Al-Najai, Mohammed, Tahir, Asma I., Baz, Batoul, Andres, Editha, Al-Boudari, Olyan, Al-Tassan, Nada, Al-Shahid, Maie, Meyer, Brian F., Dzimiri, Nduna
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.07.2014
• Subjects: atherosclerosis; Atherosclerosis - genetics; Base Sequence; chromosomes; Coronary artery disease; Coronary Artery Disease - genetics; Diabetes Mellitus, Type 2 - genetics; Dyslipidemias - genetics; Female; GATA transcription factors; GATA2 polymorphism; GATA2 Transcription Factor - genetics; Gene Frequency; genes; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Haplotypes - genetics; heterozygosity; high density lipoprotein; Humans; hypercholesterolemia; Hypercholesterolemia - complications; Hypercholesterolemia - genetics; Hyperlipidemia; Hypertension - genetics; low density lipoprotein; Male; Middle Aged; Obesity; Obesity - complications; Obesity - genetics; Polymorphism, Single Nucleotide; quantitative polymerase chain reaction; Risk; Risk Factors; Sequence Analysis, DNA; single nucleotide polymorphism; Haplotypes; T2DM; Chol; FH; HTN; LDL-C; HFH; lHDLC; HDL-C; UTR; hChol; SNP; ANOVA; GATA2 polymorphism; hTG; MI; C.I; Obesity; CON; Hyperlipidemia; CAD; S.E; Coronary artery disease; VD; O.R; TF; LD; PCR
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2014.04.064

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 (χ2=4.23; p=0.04) constructed from the eight studied SNPs and its 6-mer derivative CGGGTC (χ2=5.05; p=0.025) were associated with CAD. Obesity was associated with the 6-mer CATAAA (χ2=3.66; p=0.049), and hypercholesterolemia was linked to the 8-mer CCTGGACC (χ2=6.02; p=0.014), but most significantly so with its 5-mer derivative, CTGGA (χ2=6.75; p=0.009). On the other hand, high low density lipoprotein was linked to TGG (χ2=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. •We established a link on chr 3 to early onset CAD and familial hyperlipidemia•We performed an association study for 8 GATA2 SNPs with cardiovascular risk traits•Rs1573949 was implicated in MI, rs7431368 in low HDL, and rs10934857 in obesity•Several haplotypes constructed from the 8 SNPs were associated with disease•Our study shows an association of GATA2 with atherosclerosis metabolic risk traits