title: Several genetic polymorphisms interact with overweight/obesity to influence serum lipid levels.
abstract: BACKGROUND
  Information about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on serum lipid profiles is still scarce. The present study was undertaken to detect ten SNPs and their interactions with overweight/obesity on serum lipid levels.
  
  
  METHODS
  A total of 978 normal weight and 751 overweight/obese subjects of Bai Ku Yao were randomly selected from our previous stratified randomized cluster samples. Normal weight, overweight and obesity were defined as a body mass index (BMI) < 24, 24-28, and > 28 kg/m(2); respectively. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) A1 and ApoB levels were measured. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaII, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, the E3 ubiquitin ligase myosin regulatory light chain-interacting protein (MYLIP) rs3757354, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. The interactions were detected by factorial design covariance analysis.
  
  
  RESULTS
  The genotypic and allelic frequencies of LIPC and PCSK9 were different between normal weight and overweight/obese subjects, the genotypic frequency of LIPG and allelic frequency of MYLIP were also different between normal weight and overweight/obese subjects (P < 0.05-0.001). The levels of TC, ApoA1 (ABCA-1); TC, LDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TG, HDL-C, and ApoA1 (LIPG); TC, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); HDL-C and ApoA1 (MYLIP) in normal weight subjects were different among the genotypes (P < 0.01-0.001). The levels of LDL-C, ApoB and ApoA1/ApoB (ABCA-1); HDL-C, ApoA1, ApoB and ApoA1/ApoB (LIPC); TC, HDL-C, ApoA1 and ApoB (LIPG); TC, TG, HDL-C, LDL-C, ApoA1 and ApoB (MTHFR); TC, TG and ApoB (MYLIP); TG (PCSK9); TG, ApoA1 and ApoB (PPARD); and TC, HDL-C, LDL-C, ApoA1 and ApoB (SCARB1) in overweight/obese subjects were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1 (LDL-C and ApoA1/ApoB); LIPC (TC, LDL-C, ApoA1 and ApoB); LIPG (ApoB); MTHFR (TC, TG and LDL-C); MYLIP (TC and TG); PCSK9 (TG, HDL-C, ApoB and ApoA1/ApoB); PPARD (TG and ApoA1/ApoB); and SCARB1 (TG, ApoA1 and ApoB) interacted with overweight/obesity to influence serum lipid levels (P < 0.05-0.001).
  
  
  CONCLUSIONS
  The differences in serum lipid levels between normal weight and overweight/obese subjects might partly result from different genetic polymorphisms and the interactions between several SNPs and overweight/obesity.
authors.affiliation: Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, 22 Shuangyong Road, Nanning, Guangxi 530021, People's Republic of China. yinruixing@yahoo.com.cn
authors.forename: Rui-Xing
authors.initials: RX
authors.lastname: Yin
authors.forename: Dong-Feng
authors.initials: DF
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Miao
authors.forename: Lynn Htet Htet
authors.initials: LH
authors.lastname: Aung
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Cao
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Yan
authors.forename: Xing-Jiang
authors.initials: XJ
authors.lastname: Long
authors.forename: Wan-Ying
authors.initials: WY
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D004587:Electrophoresis, Agar Gel; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009765:Obesity / Q000097:blood / Q000235:genetics; D050177:Overweight / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008055:Lipids