Dataset Information

The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

ABSTRACT: Proprotein 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.A 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.Serum 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.The 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.

SUBMITTER: Aung LH

PROVIDER: S-EPMC3035481 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

Aung Lynn Htet Htet LH Yin Rui-Xing RX Miao Lin L Hu Xi-Jiang XJ Yan Ting-Ting TT Cao Xiao-Li XL Wu Dong-Feng DF Li Qing Q Pan Shang-Ling SL Wu Jin-Zhen JZ

Lipids in health and disease 20110113

<h4>Background</h4>Proprotein 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 populatio ...[more]

PMID: 21232153

Similar Datasets

Project description:The association of rs3757354 single nucleotide polymorphism (SNP) in the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP, also known as IDOL) gene and serum lipid levels is not well known in the general population. The present study aimed to detect the association of rs3757354 SNP and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.A total of 627 subjects of Bai Ku Yao minority and 614 participants of Han nationality were randomly selected from our stratified randomized cluster samples. Genotyping of the rs3757354 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P<0.05-0.001). The frequency of G allele was 49.92% in Bai Ku Yao and 56.27% in Han (P<0.05). The frequencies of AA, GA and GG genotypes were 25.52%, 49.12% and 25.36% in Bai Ku Yao, and 19.87%, 47.72% and 32.41% in Han (P<0.05); respectively. There were no significant differences in the genotypic and allelic frequencies between males and females in both ethnic groups. The levels of HDL-C in Bai Ku Yao were different among the genotypes (P<0.05), the G allele carriers had higher serum HDL-C levels than the G allele noncarriers. The levels TC, HDL-C and ApoAI in Han were different among the genotypes (P<0.05 for all), the participants with GA genotype had lower serum TC, HDL-C and ApoAI levels than the participants with AA genotype. These findings were found only in females but not in males. The levels of TG and HDL-C in Bai Ku Yao were correlated with the genotypes, whereas the levels of TC in Han, and TC, LDL-C in Han females were associated with the genotypes (P<0.05 for all). Serum lipid parameters were also correlated with age, sex, alcohol consumption, cigarette smoking, blood pressure, and body mass index in both ethnic groups (P<0.05-0.001).The present study suggests that the MYLIP rs3757354 SNP is associated with serum TC, HDL-C and ApoAI levels in the Bai Ku Yao and Han populations. But the association is different between the two ethnic groups.

Project description:Proprotein convertase subtilisin/kexins (PCSKs) constitute a family of nine related proteases: PCSK1-7, MBTPS1, and PCSK9. Apart from PCSK9, little is known about PCSKs in cardiovascular disease. Here, we aimed to investigate the expression landscape and druggability potential of the entire PCSK family for CVD. We applied an integrative approach, combining genetic, transcriptomic and proteomic data from three vascular biobanks comprising carotid atherosclerosis, thoracic and abdominal aneurysms, with patient clinical parameters and immunohistochemistry of vascular biopsies. Apart from PCSK4, all PCSK family members lie in genetic regions containing variants associated with human cardiovascular traits. Transcriptomic analyses revealed that FURIN, PCSK5, MBTPS1 were downregulated, while PCSK6/7 were upregulated in plaques vs. control arteries. In abdominal aneurysms, FURIN, PCSK5, PCSK7, MBTPS1 were downregulated, while PCSK6 was enriched in diseased media. In thoracic aneurysms, only FURIN was significantly upregulated. Network analyses of the upstream and downstream pathways related to PCSKs were performed on the omics data from vascular biopsies, revealing mechanistic relationships between this protein family and disease. Cell type correlation analyses and immunohistochemistry showed that PCSK transcripts and protein levels parallel each other, except for PCSK9 where transcript was not detected, while protein was abundant in vascular biopsies. Correlations to clinical parameters revealed a positive association between FURIN plaque levels and serum LDL, while PCSK6 was negatively associated with Hb. PCSK5/6/7 were all positively associated with adverse cardiovascular events. Our results show that PCSK6 is abundant in plaques and abdominal aneurysms, while FURIN upregulation is characteristic for thoracic aneurysms. PCSK9 protein, but not the transcript, was present in vascular lesions, suggesting its accumulation from circulation. Integrating our results lead to the development of a novel 'molecular' 5D framework. Here, we conducted the first integrative study of the proprotein convertase family in this context. Our results using this translational pipeline, revealed primarily PCSK6, followed by PCSK5, PCSK7 and FURIN, as proprotein convertases with the highest novel therapeutic potential.

Project description:Studies had investigated the associations between proprotein convertase subtilisin/kexin type 9 (PCSK9) E670G polymorphism and coronary artery disease (CAD) and lipid levels, but the results were controversial. Thus, we performed this meta-analysis to investigate the association between PCSK9 E670G polymorphism and lipid levels and the susceptibility to CAD.All relevant articles according to the inclusion criteria were retrieved and included in the present meta-analysis. Odds ratios (ORs) with 95 % confidence interval (CI) were used to analyze the strength of the association between PCSK9 E670G polymorphism and the susceptibility to CAD. At the same time, the pooled standardized mean difference (SMD) with 95 % CI was used for the meta-analysis of PCSK9 E670G polymorphism and lipid levels. The publication bias was examined by using Begg's funnel plots and Egger's test.A total of seventeen studies met the inclusion criteria. For CAD association, the pooled effects indicated that the G allele carriers had higher risk of CAD than non-carriers in dominant genetic model (OR:1.601, 95 % CI: 1.314-1.951, P?<?0.001), as well as in allelic genetic model (OR: 1.546, 95 % CI: 1.301-1.838, P?<?0.001). When the subgroup analysis stratified by ethnicity and HWE was performed, the positive result existed in most of the subgroups. For lipid levels association, the pooled effects indicated that the G allele carriers had higher TC and LDL-C levels than the non-carriers (for TC, SMD: 0.126, 95 % CI: 0.023-0.229, P?=?0.016; for LDL-C, SMD: 0.170, 95 % CI: 0.053-0.287, P?=?0.004, respectively). There was no difference in the levels of TG and HDL-C between the G carriers and the non-carriers in the whole population (SMD: 0.031, 95 % CI: -0.048-0.110, P?=?0.440; SMD: -0.123, 95 % CI: -0.251-0.006, P?=?0.061, respectively). When the studies were stratified by ethnicity and type of study, the G carriers had higher TC levels than the non-carriers (SMD: 0.126, 95 % CI: 0.014-0.238, P?=?0.027) in the non-Asian subgroup. The similar results existed in cohort subgroup. The association between PCSK9 E670G polymorphism and LDL-C levels was significant in all subgroups. Meanwhile, the G carriers had higher TG levels than the non-carriers (SMD: 0.113, 95 % CI: 0.012-0.214, P?=?0.028) in the case-control subgroup. AG?+?GG genotypes had lower HDL-C levels than AA genotype in Asian subgroup (SMD: -0.224, 95 % CI: -0.423- -0.025, P?=?0.027) and in case-control subgroup (SMD: -0.257, 95 % CI: -0.467--0.048, P?=?0.016).The present meta-analysis concluded that PCSK9 E670G polymorphism was associated with CAD risk and lipid levels.

Dataset Information

The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

Publications

The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets