title: Integrative mutation, haplotype and G × G interaction evidence connects ABGL4, LRP8 and PCSK9 genes to cardiometabolic risk.
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.
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Rui-Xing
authors.initials: RX
authors.lastname: Yin
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Ling
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Molecular Genetics, Medical Scientific Research Center, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Wei-Xiong
authors.initials: WX
authors.lastname: Lin
authors.affiliation: Department of Molecular Genetics, Medical Scientific Research Center, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: De-Zhai
authors.initials: DZ
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, School of Premedical Sciences, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China.
authors.forename: Shang-Ling
authors.initials: SL
authors.lastname: Pan
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism; D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism; D002268:Carboxypeptidases / Q000235:genetics* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002681:China; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D004843:Epistasis, Genetic; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics* / Q000378:metabolism; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000071449:Proprotein Convertase 9 / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D026502:LDL-Receptor Related Proteins; D014280:Triglycerides; C098773:low density lipoprotein receptor-related protein 8; D002268:Carboxypeptidases; C000627201:AGBL4 protein, human; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9