Association of the lipoprotein(a) gene (LPA) p.Ile4399Met variant with lipoprotein(a) level and cardiovascular events in patients following coronary artery bypass grafting under 65 years of age

Abstract Introduction Lipoprotein(a) (Lp[a]), a well-known risk factor for atherosclerotic cardiovascular disease, is largely determined by variation in the Lp(a) gene (LPA) locus encoding apolipoprotein(a). The LPA gene Ile4399Met (rs3798220) variant has been previously reported to have a strong association with the Lp(a) level in patients with coronary artery disease (CAD), however, its prevalence in the middle-age patients after coronary artery bypass grafting (CABG) has not been investigated. Purpose To assess the frequency of the LPA gene c.5673A>G variant (p.Ile4399Met; rs3798220) in Polish patients with CAD following CABG under 65 years of age and determined its association with laboratory and clinical variables. Materials and Methods We studied 215 patients with stable CAD, aged 59.5±4.9 years, who underwent primary and isolated CABG surgery (at age of 57.8±5.4 years), including 195 (90.8%) male. Clinical characteristics and analysis of the LPA c.5673A>G variant were performed. Results The genotype distribution was as follows: AA – 192 (89.3%), AG – 19 (8.8%), and GG – 4 (1.9%). The c.5673G allele carriers had higher Lp(a) level (106.5 [IQR 77.9-149.7] vs 10.4 [IQR 4.4-43.0] mg/dL, p<0.001) compared with non-carriers. Among the c.5673G allele carriers, Lp(a) correlated positively with pack-years of smoking (r=0.563, p=0.045) and fibrinogen (r=0.431, p=0.040), but not with low-density lipoprotein cholesterol (r=0.202, 0.368). There were no other genotype-associated differences with regard to demographic and clinical variable between carriers and non-carriers, including myocardial infarction (56.5% vs 47.9%, p=0.511), peripheral artery disease (21.7% vs 15.1%, p=0.377) and cerebrovascular events (13.0% vs 6.7%, p=0.389). Conclusions To our knowledge, this is the first report on the prevalence of LPA rs3798220 variant in patients with advanced CAD following CABG surgery under 65 years of age. We showed a relatively high (10.7%) percentage of c.5673G allele carriers who have ten times higher Lp(a) levels compared to the wild type, however, its impact on cardiovascular events requires further studies.