To the editor:
In the August 2004 issue, Guo et al.1 reported highly significant evidence for association between type 1 diabetes (T1D) and multiple polymorphisms in and near the gene SUMO4, encoding a new small ubiquitin-like modifier. The authors also showed that the 163A→G SNP (rs237025; resulting in the amino acid substitution M55V) influences immune responses by modulating NFκB activity. Both genetic and functional studies suggested that the 163G allele was associated with increased risk for T1D in a collection of European American families. But this conclusion was contradicted by the positive association with the 163A allele observed in the British data set studied by Guo et al.1 and in a separate report2 consisting primarily of a British data set. These inconsistent results raised the possibility that the reported association might be a false positive. Therefore, we tested this hypothesis in a Korean case-control cohort consisting of 386 individuals with T1D and 553 normal controls. The individuals with T1D were selected from the Korean Type 1 Diabetes Genetic Consortium3,4 using the criteria of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus5. All affected individuals were on insulin therapy upon hospital discharge. Their mean age was 13.4 years (range 0.3–23.0 years). The nondiabetic control subjects had no family history of diabetes and were selected from the same geographical area. Their mean age was 39.2 years (range 18.1–80.7 years). The GG and AG genotypes had a higher frequency in affected individuals (62.0%) than in controls (52.1%), with a relative risk of 1.5 (P < 0.003; Supplementary Table 1 online). Our results, consistent with the report by Guo et al.1, provide additional support for an association between the SUMO4 163A→G SNP and T1D. Given the association differences across populations, it will be important to investigate the SUMO4-T1D association in other populations to understand the mechanisms responsible for these population differences, including gene-gene and gene-environment interactions.
Note: Supplementary information is available on the Nature Genetics website.
References
Guo, D. et al. Nat. Genet. 36, 837–841 (2004).
Bohren, K.M. et al. J. Biol. Chem. 279, 27233–27238 (2004).
Park, Y. & Eisenbarth, G.S. Diabetes Metab. Res. Rev. 17, 2–11 (2001).
Park, Y. Diabetes Res. Clin. Pract. 66, S19–S25 (2004).
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 23, S4–S19 (2000).
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Park, Y., Park, S., Kang, J. et al. Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes. Nat Genet 37, 112 (2005). https://doi.org/10.1038/ng0205-112a
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DOI: https://doi.org/10.1038/ng0205-112a
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