The effect of the LPA gene on aortic valve calcification in a Portuguese population

Abstract Introduction Aortic valve calcium (AVC) deposition is one of the mechanisms behind aortic sclerosis and stenosis. There is a known association between LPA gene rs3798220 T>C polymorphism and the development of severe aortic stenosis. However, it is still unknown if it has been a driving factor since the early stages of the disease. Objective Investigate, in our population, the association between the LPA gene variant rs3798220 T>C and aortic valve calcification. Methods AVC was measured in 451 consecutive individuals from the prospective arm of the GENEMACOR study with a mean age of 63.4±9.7 years, 58.8% male. AVC score was performed by cardiac computed tomography and reported as Agatston units. Results were separated into two groups (Group A: AVC=0; Group B: AVC>0). Lp(a) levels were analyzed in the different groups. Each individual was genotyped for LPA rs3798220 T>C. This variant has a minor allele frequency (MAF)<2%; hence, the risk homozygous CC is a rare genotype, and we used the heterozygous CT in our analysis. The bivariate and multivariate logistic regression analysis evaluated the presence of AVC adjusting to traditional risk factors (TRFs) and the LPA heterozygous genotype (CT). Results LP(a) levels were higher in the CT allele versus the homozygous TT, but this difference did not reach a statistical significance. After multivariate analysis, the heterozygous LPA rs3798220 T>C polymorphism remained an independent risk factor for the presence of aortic valve calcification (OR=12.14, p=0.002) together with age (OR=1.13, p<0.0001), arterial hypertension (AHT) (OR=1.96, p=0.006) and alcohol consumption (OR=2.46, p=0.016). Conclusion The LPA gene variant rs3798220 T>C is associated with the presence of aortic valve calcification in a Portuguese population. In such an age-dependent disease as aortic stenosis, the inversion in the age pyramid will see a dramatic increase in the prevalence of aortic stenosis. The early identification of high-risk individuals might enable prompt traditional risk factors control and disease prevention. Larger population studies may help to determine if this difference is driven by Lp(a) levels.