Polymorphisms in PCSK9, LDLR, BCMO1, SLC12A3, and KCNJ1 are Associated with Serum Lipid Profile in Chinese Han Population.

Zheng Li,Song Lei,Lei Yang,Tianyu Zhao,Xiaohua Tan,Liu Huang

doi:10.3390/ijerph16173207

Abstract

Unfavorable serum lipid levels are the most important risk factors for coronary artery disease (CAD), cerebral infarction, and other cardiovascular and cerebrovascular diseases. This study included 2323 Han Chinese in southern China. We collected medical reports, lifestyle details, and blood samples of individuals and used the polymerase chain reaction-ligase detection reaction method to genotype single-nucleotide polymorphisms (SNPs). Two SNPs showed a strong evidence of association with total cholesterol (TC): rs1003723 and rs6413504 in the low-density lipoproteins receptor (LDLR). Two SNPs in LDLR showed a strong evidence of association with low-density lipoprotein cholesterol (LDL-C), rs1003723 and rs6413504. Two SNPs showed a strong evidence of association with triglycerides (TG), namely, rs662145 in pro-protein convertase subtilisin-kexin type 9 (PCSK9) and rs11643718 in the solute carrier family 12 member 3 (SLC12A3). For the TC, LDL-C, and TG levels, these SNPs generated strong combined effects on these lipid levels. For each additional dangerous gene, TC increased by 0.085 mmol/L (p = 7.00 × 10−6), and LDL-C increased by 0.075 mmol/L (p = 9.00 × 10−6). The TG increased by 0.096 mmol/L (p = 2.90 × 10−5). Compared with those bearing no risk alleles, the risk of hypertriglyceridemia, hypercholesterolemia, and dyslipidemia increased in those with two or more risk alleles and one risk gene. Polymorphisms of PCSK9, LDLR, and SLC12A3 were associated with the plasma lipid levels in people in southern China. These results provide a theoretical basis for gene screening and the prevention of dyslipidemia.

Highlights

Epidemiological studies have shown that among the risk factors of coronary artery disease (CAD), cerebral infarction, including other cardiovascular and cerebrovascular diseases, dyslipidemia is an important factor [1,2,3]
The minor allele frequency (MAF) of each single-nucleotide polymorphisms (SNPs) was more than 5% to ensure that this study had enough statistical power (Table 2)
Low-density lipoprotein cholesterol receptor-related proteins (LRPs) are transmembrane receptors involved in endocytosis, cell signaling, and trafficking of other cellular proteins, which is produced in the endoplasmic reticulum of the hepatocytes, and attain maturity in the Golgi apparatus, get expressed on the cell surface

Summary

Introduction

Epidemiological studies have shown that among the risk factors of coronary artery disease (CAD), cerebral infarction, including other cardiovascular and cerebrovascular diseases, dyslipidemia is an important factor [1,2,3]. According to recent research of genome-wide association studies (GWAS), a large number of single-nucleotide polymorphisms (SNPs) have been authenticated, which are related to lipid levels in Caucasian-descent populations [4,8,9,10,11,12,13,14]. These SNPs were originally identified among the ancestors of Europeans, whereas among Asian populations, especially Chinese, just a handful of genes were assessed. Whether these variants confer the risk of dyslipidemia on the Han Chinese population, with its different demographic and lifestyles, has hardly been explored

Methods

Results

Conclusion