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

Genetic association analysis of LARS2 with type 2 diabetes.

Author information

1
Department of Molecular Cell Biology, Leiden University Medical Center (LUMC), 2300RC Leiden, the Netherlands.

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.

PMID:
19847392
PMCID:
PMC2789927
DOI:
10.1007/s00125-009-1557-7
[Indexed for MEDLINE]
Free PMC Article

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