Association of rs3798220 Polymorphism with Cardiovascular Incidents in Individuals with Elevated Lp(a)

<b>Background/Objectives</b>: Lipoprotein (a) [Lp(a)] plays a significant role in atherosclerosis and cardiovascular disease (CVD). Genetic regulation of Lp(a) involves variations in the apo(a) <i>LPA</i> gene, as specific polymorphisms like rs10455872 and rs3798220, both linked to higher Lp(a) levels and CVD. CVD remains the leading global cause of death, with high Lp(a) levels increasingly recognized as a significant factor in younger patients with no other CVD risk factors. We aimed to evaluate the association of <i>LPA</i> genetic variations with Lp(a) levels and its effect on cardiovascular risk as there are existing inconsistent findings. <b>Methods</b>: This case-control study included 251 subjects with a median age of 52 years (interquartile range, IQR = 17) and elevated Lp(a) levels. Cases were subjects who experienced early cardiovascular incidents (women < 65, men < 55 years old), and the control group included subjects without such history. Genotyping of <i>LPA</i> gene polymorphisms (rs10455872 and rs3798220) was performed, and demographic data with Lp(a) levels were collected. To evaluate the association between the <i>LPA</i> genotypes and the risk of cardiovascular incidents (CVI), several logistic regression models were performed. The cut-off points for Lp(a) levels were determined using diagnostic test accuracy measures. <b>Results</b>: The rs3798220-<i>C</i> allele was associated with higher Lp(a) levels (288 ± 166 nmol/L in cases vs. 189 ± 102 nmol/L in controls, <i>p</i> < 0.001) and myocardial infarction (53% in cases vs. 36% in controls, <i>p</i> = 0.036). Among cases, 28.9% carried the rs3798220-<i>C</i> allele, compared to 18.7% in controls. The rs10455872-G allele was slightly more prevalent in controls (34.15% vs. 29.69%) but without further significant associations. In this study, the cut-off Lp(a) value of 151 nmol/L, for patients with a positive family history of early CVD, is associated with a higher chance of developing CVI. <b>Conclusions</b>: This study demonstrates an association between the <i>LPA</i> rs3798220-<i>C</i> allele and higher Lp(a) levels, as well as an increased risk of early onset myocardial infarction. However, the obtained association should further be evaluated at a much larger scale.