Genetic variants in selenoprotein P plasma 1 gene (SEPP1) are associated with fasting insulin and first phase insulin response in Hispanics

Jacklyn N. Hellwege, Nicholette D. Palmer, Julie T. Ziegler, Carl D. Langefeld, Carlos Lorenzo, Jill M. Norris, Toshinari Takamura, Donald W. Bowden

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Context: 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. Participants and measures: 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). Design: 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 (r2=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.

Original languageEnglish (US)
Pages (from-to)33-39
Number of pages7
JournalGene
Volume534
Issue number1
DOIs
StatePublished - Jan 15 2014

Keywords

  • Acute insulin response (AIR)
  • Fibrinogen
  • Hispanic Americans
  • Insulin resistance
  • Selenium
  • Selenoproteins

ASJC Scopus subject areas

  • Genetics

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