Genetic Characteristics Contributing to Lipoprotein(a) Levels in the Japanese Population

抄録

Objective: Lipoprotein(a) [Lp(a)] is an important causal factor of atherosclerosis and is heritable. The effect size of single nucleotide polymorphisms (SNPs) on Lp(a) among Japanese is not well understood.
Materials and methods: Genotype imputation of common SNPs within the Lp(a) locus was performed based on SNP data used to perform direct genotyping with the Japonica Array^® in 126 Japanese individuals with significantly high (< 70 mg/dL) or low (< 5 mg/dL) levels of Lp(a). In total, 187 SNPs with high imputation quality were identified at the LPA locus. The number of SNPs with high linkage disequilibrium was narrowed to 17. The chi-square test was used to identify associations between SNPs and Lp(a) levels, and a linear regression analysis was performed to evaluate the effect size of each SNP on Lp(a) levels. Furthermore, the polygenic risk score (PRS) of Lp(a) was calculated using statistically significant SNPs.
Results: rs7454595, rs7765803, rs77182492, rs1652507, rs1321195 and rs74734070 were significantly associated with Lp(a) levels. However, the effect size of rs7454595, rs77182492, and rs74734070 on the levels in other ethnicities was unclear. Additionally, the absolute effect sizes of each SNP on Lp(a) levels ranged from 27.34 to 47.04 mg/dL per allele. The high Lp(a) group had a significantly higher PRS than the low Lp(a) group. A significant trend was observed in Lp(a) levels according to the PRS quartiles.
Conclusions: There are shared and specific genetic characteristics that contribute to Lp levels among different ethnicities, and a few SNPs may partly explain the differences in Lp(a) levels among Japanese.