Over the past several decades, numerous studies have established that increased levels of apolipoprotein(a) [Lp(a)] in plasma are associated with development of coronary heart disease (CHD). Upon discovery of the apo(a) gene (LPA), which was considered one of the most polymorphic transcribed genes in the human genome, researchers reported several polymorphism in LPA gene which associated with CHD and plasma Lp(a) levels. Recently, a single nucleotide polymorphism (SNP) rs3798220, also known as Ile4399Met, encoding an isoleucine to methionine substitution located in the protease-like domain of apo(a) at amino acid 4399 have been shown to be associated with CHD and plasma Lp(a) levels in Caucasians.

This study investigated the association of SNP rs3798220 with plasma Lp(a) in a large scale of Berkeley HeartLab samples representing genetically diverse populations. The study showed that the heterozygous carriers of SNP rs3798220 (Ile/Met) had 2.8 fold higher serum Lp(a) levels with a mean of 64.3 mg/dL and 95% CI [63.1, 65.5] (p = 0.0000) compare to serum Lp(a) levels of homozygous non-carriers (Ile/Ile) having a mean of 33.4mg/dL and 95% CI [33.0, 33.6].

Interestingly, this study showed that the homozygous carriers (Met/Met) have 2.1 fold lower plasma Lp(a) than non-carriers (Ile/Ile) with a mean of 24.5mg/dL (p = 0.0034) and 6 fold lower than heterozygous carries (Ile/Met).

This study also investigated the association of the same SNP with other biomarkers and concluded that there was a strong and clinically significant association between carriers of Ile/Met (genotype ag) and Met/Met (genotype gg) with high serum Triglyceride levels.