Genetic association analysis of LARS2 with type 2 diabetes

Diabetologia. 2010 Jan;53(1):103-10. doi: 10.1007/s00125-009-1557-7. Epub 2009 Oct 22.

Abstract

Aims/hypothesis: LARS2 has been previously identified as a potential type 2 diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant (minor allele frequency [MAF] 3.0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and common variants in LARS2 (MAF > 5%) to type 2 diabetes risk.

Methods: We combined genome-wide association data (n = 10,128) from the DIAGRAM consortium with independent data derived from a tagging single nucleotide polymorphism (SNP) approach in Dutch individuals (n = 999) and took forward two SNPs of interest to replication in up to 11,163 Dutch participants (rs17637703 and rs952621). In addition, because inspection of genome-wide association study data identified a cluster of low-frequency variants with evidence of type 2 diabetes association, we attempted replication of rs9825041 (a proxy for this group) and the previously identified H324Q variant in up to 35,715 participants of European descent.

Results: No association between the common SNPs in LARS2 and type 2 diabetes was found. Our replication studies for the two low-frequency variants, rs9825041 and H324Q, failed to confirm an association with type 2 diabetes in Dutch, Scandinavian and UK samples (OR 1.03 [95% CI 0.95-1.12], p = 0.45, n = 31,962 and OR 0.99 [0.90-1.08], p = 0.78, n = 35,715 respectively).

Conclusions/interpretation: In this study, the largest study examining the role of sequence variants in LARS2 in type 2 diabetes susceptibility, we found no evidence to support previous data indicating a role in type 2 diabetes susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Amino Acid Substitution
  • Amino Acyl-tRNA Synthetases / genetics*
  • Amino Acyl-tRNA Synthetases / metabolism
  • Body Mass Index
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / enzymology*
  • Diabetes Mellitus, Type 2 / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Linkage Disequilibrium
  • Mitochondrial Proteins / genetics
  • Polymorphism, Single Nucleotide

Substances

  • Mitochondrial Proteins
  • Amino Acyl-tRNA Synthetases
  • LARS2 protein, human