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Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk.
- Source :
-
Scientific reports [Sci Rep] 2016 Nov 17; Vol. 6, pp. 37375. Date of Electronic Publication: 2016 Nov 17. - Publication Year :
- 2016
-
Abstract
- This study is expected to investigate the association of ATP/GTP binding protein-like 4 (AGBL4), LDL receptor related protein 8 (LRP8) and proprotein convertase subtilisin/kexin type 9 (PCSK9) gene single nucleotide variants (SNVs) with lipid metabolism in 2,552 individuals (Jing, 1,272 and Han, 1,280). We identified 12 mutations in this motif. The genotype and allele frequencies of these variants were different between the two populations. Multiple-locus linkage disequilibrium (LD) elucidated the detected sites are not statistically independent. Possible integrative haplotypes and gene-by-gene (G × G) interactions, comprising mutations of the AGBL4, LRP8 and PCSK9 associated with total cholesterol (TC, AGBL4 G-G-A, PCSK9 C-G-A-A and G-G-A-A-C-A-T-T-T-G-G-A), triglyceride (TG, AGBL4 G-G-A, LRP8 G-A-G-C-C, PCSK9 C-A-A-G, A-A-G-G-A-G-C-C-C-A-A-G and A-A-G-G-A-G-C-C-C-G-A-A), HDL cholesterol (HDL-C, AGBL4 A-A-G and A-A-G-A-A-G-T-C-C-A-A-G) and the apolipoprotein(Apo)A1/ApoB ratio (A1/B, PCSK9 C-A-A-G) in Jing minority. However, in the Hans, with TG (AGBL4 G-G-A, LRP8 G-A-G-C-C, PCSK9 C-A-A-G, A-A-G-G-A-G-C-C-C-A-A-G and A-A-G-G-A-G-C-C-C-G-A-A), HDL-C (LRP8 A-A-G-T-C), LDL-C (LRP8 A-A-G-T-C and A-A-G-A-A-G-T-C-C-A-A-G) and A1/B (LRP8 A-C-A-T-T and PCSK9 C-A-A-G). Association analysis based on haplotype clusters and G × G interactions probably increased power over single-locus tests especially for TG.
- Subjects :
- Adult
Aged
Alleles
Apolipoprotein A-I genetics
Apolipoprotein A-I metabolism
Apolipoproteins B genetics
Apolipoproteins B metabolism
Carboxypeptidases metabolism
Cardiovascular Diseases ethnology
Cardiovascular Diseases metabolism
Cardiovascular Diseases pathology
China
Cholesterol, HDL blood
Cholesterol, LDL blood
Cohort Studies
Ethnicity
Female
Gene Frequency
Genetic Association Studies
Haplotypes
Humans
LDL-Receptor Related Proteins metabolism
Linkage Disequilibrium
Lipid Metabolism
Male
Metabolic Syndrome ethnology
Metabolic Syndrome metabolism
Metabolic Syndrome pathology
Middle Aged
Proprotein Convertase 9 metabolism
Risk
Triglycerides blood
Carboxypeptidases genetics
Cardiovascular Diseases genetics
Epistasis, Genetic
LDL-Receptor Related Proteins genetics
Metabolic Syndrome genetics
Polymorphism, Single Nucleotide
Proprotein Convertase 9 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 27853278
- Full Text :
- https://doi.org/10.1038/srep37375