| Summary: | Subclinical atherosclerosis (SA) is the presence of coronary calcification in the absence of cardiovascular symptoms, and it usually progresses to atherosclerotic disease. Studies have shown an association of osteoprotegerin gene (<i>OPG</i>) variants with calcification process in cardiovascular diseases; however, to this day there are no studies that evaluate individuals in the asymptomatic stage of atherosclerotic disease. Therefore, the purpose of this study was to analyze the association of four genetic variants and haplotypes of the <i>OPG</i> gene with the development of SA, through TaqMan genotyping assays. We also aimed to identify potential response elements for transcription factors in these genetic variants. The study included 1413 asymptomatic participants (1041 were controls and 372 were individuals with SA). The rs3102735 polymorphism appeared as a protective marker (OR = 0.693; 95% CI = 0.493–0.974; <i>p</i><sub>heterozygote</sub> = 0.035; OR = 0.699; 95% CI = 0.496–0.985; <i>p</i><sub>codominant</sub> <sub>1</sub> = 0.040) and two haplotypes were associated with SA, one as a decreased risk: <i>GACC</i> (OR = 0.641, 95% CI = 0.414–0.990, <i>p</i> = 0.045) and another as an increased risk: <i>GACT</i> (OR = 1.208, 95% CI = 1.020–1.431, <i>p</i> = 0.029). Our data suggest a lower risk of SA in rs3102735 <i>C</i> carriers in a representative sample of Mexican mestizo population.
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