Abstract
BackgroundProprotein convertase subtilisin-like kexin type 9 (PCSK9) plays a key role in regulating plasma low-density lipoprotein cholesterol (LDL-C) levels. However, the association of E670G (rs505151) polymorphism in the PCSK9 gene and serum lipid levels is inconsistent in several previous studies. The present study was undertaken to detect the association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.MethodsA total of 649 subjects of Bai Ku Yao and 646 participants of Han were randomly selected from our previous samples. Genotypes of the PCSK9 E670G polymorphism were determined via polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.ResultsSerum levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of G allele was 2.00% in Bai Ku Yao and 4.80% in Han (P < 0.01). There was significant difference in the genotypic and allelic frequencies between Bai Ku Yao and Han (P < 0.01); between normal LDL-C (≤ 3.20 mmol/L) and high LDL-C subgroups (> 3.20 mmol/L, P < 0.01) in Bai Ku Yao; and between normal HDL-C (≥ 0.91 mmol/L) and low HDL-C (< 0.91 mmol/L, P < 0.05), between normal ApoAI (≥ 1.00 g/L) and low ApoAI (< 1.00 g/L, P < 0.05), or between normal ApoAI/ApoB ratio (≥ 1.00) and low ApoAI/ApoB ratio (< 1.00, P < 0.01) subgroups in Han. The G allele carriers in Han had higher serum HDL-C levels and the ratio of ApoAI to ApoB than the G allele noncarriers. The G allele carriers in Han had higher serum HDL-C and ApoAI levels than the G allele noncarriers in males (P < 0.05 for each), whereas the G allele carriers had lower serum ApoB levels and higher the ratio of ApoAI to ApoB than the G allele noncarriers in females (P < 0.05 for all). Serum HDL-C and ApoAI levels in Han were correlated with genotypes (P < 0.05) in males, and serum ApoB levels and the ratio of ApoAI to ApoB were associated with genotypes (P < 0.05) in females.ConclusionsThe PCSK9 E670G polymorphism is mainly associated with some serum lipid parameters in the Han population. The G allele carriers had higher serum HDL-C and ApoAI levels in males, and lower serum ApoB levels and higher the ApoAI/ApoB ratio in females than the G allele noncarriers.
Highlights
Abnormalities in lipid metabolism such as elevated serum levels of total cholesterol (TC) [1], triglyceride (TG) [2], low-density lipoprotein cholesterol (LDL-C) [3], and apolipoprotein (Apo) B [4], or low levels of high-density lipoprotein cholesterol (HDL-C) and ApoAI [4,5,6] are considered as major risk factors for coronary artery disease (CAD)
The levels of height, weight, systolic blood pressure, pulse pressure, serum TC, HDL-C, LDL-C, ApoAI were lower in Bai Ku Yao than in Han Chinese (P < 0.01-0.001), whereas the percentage of subjects who consumed alcohol was higher in Bai Ku Yao than in Han (P < 0.001)
Males and females in both ethnic groups; respectively, we showed that serum HDL-C and ApoAI levels in Han but not in Bai Ku Yao were correlated with genotypes (P < 0.05) in males, and serum ApoB levels and the ratio of ApoAI to ApoB were associated with genotypes (P < 0.05, Table 5) in females
Summary
Abnormalities in lipid metabolism such as elevated serum levels of total cholesterol (TC) [1], triglyceride (TG) [2], low-density lipoprotein cholesterol (LDL-C) [3], and apolipoprotein (Apo) B [4], or low levels of high-density lipoprotein cholesterol (HDL-C) and ApoAI [4,5,6] are considered as major risk factors for coronary artery disease (CAD). It is generally agreed that dyslipidemia is complex and the result of the interactions [7,8] of multiple genes [9,10,11] and multiple environmental factors [12,13] Both family and twin studies have consistently shown that 40-60% of the interindividual variation in plasma lipid phenotypes is genetic in etiology [14,15,16]. The gene produces a mRNA of 3636 bp encoding a 692-amino acid glycoprotein This protein, called neural apoptosis regulated convertase, is a serine protease belonging to the protease K subfamily of subtilases. The present study was undertaken to detect the association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations
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