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

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.

The c.*52 A/G and c.*773 A/G Genetic Variants in the UTR′3 of the LDLR Gene Are Associated with the Risk of Acute Coronary Syndrome and Lower Plasma HDL-Cholesterol Concentration

“…It is important to notice that the allele distribution of these polymorphisms varies according to the ethnic origin of the study populations. In this context, data obtained from the National Center for Biotechnology Information revealed that the individuals from Los Angeles with Mexican ancestry, Mexican mestizos, Caucasian, and Africans had a lower frequency of the c.*52 A allele (26,23,23, and 15%, respectively) than Asians (41%). Moreover, Mexican mestizos, Europeans, Africans, as well as individuals from Los Angeles with Mexican ancestry, have a lower frequency of the c.*773 G allele (23,22,16, and 26%, respectively) than the Asian population (41%) [31].…”

“…According to data in the literature, the impact of the LDLR gene polymorphisms on lipid plasma concentration has been proposed as the mechanism that explains the relationship between these SNPs and the higher risk of developing familial hypercholesterolemia [ 7 , 8 ]. In this context, recent studies have associated the LDLR polymorphisms (c.*52 A/G , c.*504 A/G , and c.*773 A/G ) with low levels of plasma lipids and the risk of developing familial hypercholesterolemia [ 9 , 10 , 11 , 23 ]. For example, Li et al reported that c.*773 G/G genotype is associated with decreased plasma levels of HDL-C in healthy individuals of China [ 23 ].…”

“…In this context, recent studies have associated the LDLR polymorphisms (c.*52 A/G , c.*504 A/G , and c.*773 A/G ) with low levels of plasma lipids and the risk of developing familial hypercholesterolemia [ 9 , 10 , 11 , 23 ]. For example, Li et al reported that c.*773 G/G genotype is associated with decreased plasma levels of HDL-C in healthy individuals of China [ 23 ]. In the same way, van Zyl et al documented that c.*52 A/A and c.*504 A/A genotypes are associated with increased levels of LDL-C in the healthy black South African population [ 11 ].…”

“…Finally, in our study, the c.*52 A/G and c.*773 A/G polymorphisms were associated with the presence of ACS; however, the participation of these polymorphisms is controversial in other populations. We think that the association of the LDLR polymorphisms with ACS could be due to the role of this receptor in the regulation of the circulating cholesterol-containing lipoprotein particles, which is, in turn, an important cardiovascular risk factor [ 11 , 23 ]. It is important to notice that the allele distribution of these polymorphisms varies according to the ethnic origin of the study populations.…”

Two-Way Impacts Between Macrophages on Vascular Endothelium and Characteristics of TCM Syndromes in Dyslipidemic Mice with the Phlegm-Dampness Retention syndrome and the Spleen and Kidney Yang Deficiency syndrome Using RNA-Seq

“…As the life quality increases and dietary pattern changes, multiple factors give rise to the growing morbidity of dyslipidemia. An epidemiological study shows that dyslipidemia closely links to cardiovascular and cerebrovascular diseases, including coronary atherosclerotic heart disease and cerebral infarction [ [1]]. It is estimated that the overall morbidity of dyslipidemia in Chinese adults reaches 40.40% and continues to rise [ [2]].…”