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.