title: Genetic variants in selenoprotein P plasma 1 gene (SEPP1) are associated with fasting insulin and first phase insulin response in Hispanics.
abstract: BACKGROUND
  Insulin resistance is not fully explained on a molecular level, though several genes and proteins have been tied to this defect. Knockdowns of the SEPP1 gene, which encodes the selenoprotein P (SeP) protein, have been shown to increase insulin sensitivity in mice. SeP is a liver-derived plasma protein and a major supplier of selenium, which is a proposed insulin mimetic and antidiabetic agent.
  
  
  OBJECTIVE
  SEPP1 single nucleotide polymorphisms (SNPs) were selected for analysis with glucometabolic measures.
  
  
  METHODS
  The study included1424 Hispanics from families in the Insulin Resistance Atherosclerosis Family Study (IRASFS). Additionally, the multi-ethnic Insulin Resistance Atherosclerosis Study was used. A frequently sampled intravenous glucose tolerance test was used to obtain precise measures of acute insulin response (AIR) and the insulin sensitivity index (SI).
  
  
  METHODS
  21 SEPP1 SNPs (tagging SNPs (n=12) from HapMap, 4 coding variants and 6 SNPs in the promoter region) were genotyped and analyzed for association.
  
  
  RESULTS
  Two highly correlated (r(2)=1) SNPs showed association with AIR (rs28919926; Cys368Arg; p=0.0028 and rs146125471; Ile293Met; p=0.0026) while rs16872779 (intronic) was associated with fasting insulin levels (p=0.0097). In the smaller IRAS Hispanic cohort, few of the associations seen in the IRASFS were replicated, but meta-analysis of IRASFS and all 3 IRAS cohorts (N=2446) supported association of rs28919926 and rs146125471 with AIR (p=0.013 and 0.0047, respectively) as well as rs7579 with SI (p=0.047).
  
  
  CONCLUSIONS
  Overall, these results in a human sample are consistent with the literature suggesting a role for SEPP1 in insulin resistance.
authors.affiliation: Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, USA; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC, USA; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jacklyn N
authors.initials: JN
authors.lastname: Hellwege
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.forename: Julie T
authors.initials: JT
authors.lastname: Ziegler
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Carlos
authors.initials: C
authors.lastname: Lorenzo
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Toshinari
authors.initials: T
authors.lastname: Takamura
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005215:Fasting / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006630:Hispanic or Latino; D006801:Humans; D007328:Insulin / Q000097:blood / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051149:Selenoprotein P / Q000235:genetics*
chemical_list: D007328:Insulin; D051149:Selenoprotein P
keywords: AA; AIR; Acute Insulin Response; Acute insulin response (AIR); African American; ApoB; Apolipoprotein B; BMI; Body Mass Index; DI; Disposition Index; EA; European American; FSIGT; Fibrinogen; Frequently Sampled Intravenous Glucose Tolerance Test; HA; HDL; HOMA-IR; High-density Lipoprotein; Hispanic American; Hispanic Americans; Homeostasis model assessment of insulin resistance; IL6; IRAS; IRASFS; Insulin Resistance Atherosclerosis Family Study; Insulin Resistance Atherosclerosis Study; Insulin Sensitivity Index; Insulin resistance; Interleukin 6; LDL; Low-density Lipoprotein; MAF; MCRI; Metabolic Clearance Rate of Insulin; Minor Allele Frequency; PAI-1; Plasminogen Activator Inhibitor-1; S(I); SAT; SNP; SOLAR; SeP; Selenium; Selenoprotein P; Selenoproteins; Sequential Oligogenic Linkage Analysis Routines; Single Nucleotide Polymorphism; Subcutaneous Adipose Tissue; T2D; TNF; Tumor Necrosis Factor; Type 2 Diabetes Mellitus; UTR; VAT; Visceral Adipose Tissue; WHR; Waist:Hip ratio; untranslated region