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Single nucleotide polymorphisms in genes encoding LKB1 (STK11), TORC2 (CRTC2) and AMPK alpha2-subunit (PRKAA2) and

Parvaneh Keshavarz1, Hiroshi Inoue, Naoto Nakamura

  • 1Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3-18-15, Kuramoto-cho, Tokushima 770-8503, Japan.

Molecular Genetics and Metabolism
|October 24, 2007
PubMed

Insights

Genetic variations in the LKB1-AMPK-TORC2 pathway may weakly influence type 2 diabetes risk in Japanese individuals. Gene-gene interactions between STK11 and CRTC2 suggest a combined effect on susceptibility.

Area of Science:

  • Genetics
  • Metabolic Diseases
  • Molecular Biology

Background:

  • The LKB1-AMPK-TORC2 signaling pathway is crucial for liver glucose homeostasis and mediates the effects of antidiabetic drugs.
  • Understanding the genetic basis of type 2 diabetes susceptibility is essential for developing targeted therapies.

Purpose of the Study:

  • To investigate whether genetic variations in STK11 (LKB1) and CRTC2 (TORC2) genes contribute to type 2 diabetes risk.
  • To replicate previously reported associations between PRKAA2 (AMPK alpha2-subunit) variants and type 2 diabetes.

Main Methods:

  • A case-control study was conducted in 1787 unrelated Japanese individuals.
  • Screening for genetic variants in STK11 and CRTC2, including single nucleotide polymorphisms (SNPs).
  • Replication analysis of PRKAA2 haplotype and SNP associations with type 2 diabetes and serum cholesterol levels.

Main Results:

  • Nominal associations were found for an intronic STK11 SNP (rs741765) and a non-synonymous CRTC2 SNP (rs1418442), but these did not survive multiple testing correction.
  • Replication of the PRKAA2 haplotype association with type 2 diabetes was unsuccessful.
  • Evidence of gene-gene interaction between STK11 and CRTC2 in influencing type 2 diabetes susceptibility was observed.

Conclusions:

  • Genetic variants in LKB1-AMPK-TORC2 pathway components may have a minor role in type 2 diabetes development in the Japanese population.
  • Gene-gene interactions, particularly between STK11 and CRTC2, might be important for understanding type 2 diabetes susceptibility.

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