Genetics
The rs3798220-C LPA variant tracks with higher Lp(a) and more early myocardial infarction in a 251-patient case-control study (Diagnostics 2025)
Original title: Association of rs3798220 Polymorphism with Cardiovascular Incidents in Individuals with Elevated Lp(a)
In this case-control study of 251 subjects with elevated Lp(a) (median age 52), carriers of the rs3798220-C LPA allele had higher Lp(a) levels than non-carriers (288 plus/minus 166 nmol/L vs. 189 plus/minus 102 nmol/L, P < 0.001) and a higher rate of myocardial infarction (53% vs. 36%, P = 0.036). The C allele was present in 28.9% of cases with early cardiovascular incidents versus 18.7% of controls, while the rs10455872-G allele showed no significant association with outcomes. A cut-off Lp(a) of 151 nmol/L was linked to greater risk of cardiovascular incidents in patients with a family history of early disease. The authors note the modest sample size and call for validation in a larger cohort before this variant informs risk assessment.
Original abstract
Background/Objectives: 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) LPA 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 LPA genetic variations with Lp(a) levels and its effect on cardiovascular risk as there are existing inconsistent findings. Methods: 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 LPA gene polymorphisms (rs10455872 and rs3798220) was performed, and demographic data with Lp(a) levels were collected. To evaluate the association between the LPA 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. Results: The rs3798220-C allele was associated with higher Lp(a) levels (288 ± 166 nmol/L in cases vs. 189 ± 102 nmol/L in controls, p < 0.001) and myocardial infarction (53% in cases vs. 36% in controls, p = 0.036). Among cases, 28.9% carried the rs3798220-C 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. Conclusions: This study demonstrates an association between the LPA rs3798220-C 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.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.