Association of type 2 diabetes susceptibility genes (TCF7L2, SLC30A8, PCSK1 and PCSK2) and proinsulin conversion in a Chinese population

Mol Biol Rep. 2012 Jan;39(1):17-23. doi: 10.1007/s11033-011-0705-6. Epub 2011 Mar 25.

Abstract

TCF7L2 and SLC30A8 have been found to be associated with type 2 diabetes mellitus (T2DM) as well as with impaired proinsulin processing recently, enzymes encoded by PCSK1 and PCSK2 are reported to play an important role in the process of proinsulin conversion. To investigate whether the single nucleotide polymorphisms (SNPs) of TCF7L2, SLC30A8, PCSK1 and PCSK2 were associated with T2DM as well as with proinsulin conversion in a Han Chinese population from Chongqing. A case-control study was performed in Han Chinese subjects with normal control (n=152) and T2DM (n=227), we genotyped rs7903146 and rs11196218 at TCF7L2, rs13266634 at SLC30A8, rs3811951 at PCSK1 and rs2021785 at PCSK2. Plasma levels of proinsulin were measured with an Enzyme Linked Immunosorbent Assay (ELISA). Genotype distribution and associations with T2DM and fasting levels of proinsulin and proinsulin/insulin ratios were analyzed. We confirmed the association of risk allele of rs2021785 at PCSK2 with type 2 diabetes also existed in Han Chinese population [OR=1.4489 with 95% CI (1.0285, 2.0412), P=0.0335]. Rs13266634 at SLC30A8 had a tendency to be associated with fasting plasma levels of proinsulin (P=0.0639 in additive model). We did not find the significant association between other SNPs and T2DM or fasting levels of proinsulin or proinsulin/insulin ratios. Our results provide evidence that the association of PCSK2 and T2DM was also existed in Han Chinese population in Chongqing. We were underpowered to detect the association between other SNPs and T2DM or proinsulin conversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics
  • Case-Control Studies
  • Cation Transport Proteins / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Proinsulin / genetics
  • Proinsulin / metabolism*
  • Proprotein Convertase 1 / genetics*
  • Proprotein Convertase 1 / metabolism
  • Proprotein Convertase 2 / genetics*
  • Proprotein Convertase 2 / metabolism
  • Transcription Factor 7-Like 2 Protein / genetics*
  • Zinc Transporter 8

Substances

  • Cation Transport Proteins
  • SLC30A8 protein, human
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Zinc Transporter 8
  • Proinsulin
  • Proprotein Convertase 1
  • Proprotein Convertase 2