Abstract
Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1, also known as PC-1) inhibits insulin signal transduction pathway(s). Previous studies have demonstrated the K121Q variant of the ENPP1 gene to have a significant functional role in determining susceptibility to insulin resistance and type 2 diabetes (T2D). To assess whether the K121Q variant has any impact on T2D in Japanese, we undertook an extensive case-control association study using a total of 911 unrelated Japanese T2D patients and 876 control subjects. No significant difference was observed in either genotype distribution (P=0.95) or allele frequency (P=0.83) between T2D and control groups. Notably, the frequency of the ancestral Q121 allele, which is also present in other primates, was quite high in African-Americans, and showed a marked ethnic variation (77.3% in African-Americans, 16.7% in European Americans, 10.5% in Japanese and 4.2% in Han Chinese). Consequently, the pairwise FST value (a classic measure of genetic distance between pairs of population) showed highly significant differentiations between African-American and non-African-American populations (FST>0.3). Our results indicated that the K121Q variant of the ENPP1 gene has very little, if any, impact on T2D susceptibility in Japanese, but may play a role in the inter-ethnic variability in insulin resistance and T2D.
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01 July 2006
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Acknowledgements
We would like to thank our patients and volunteer blood donors for participating in this study. We thank the many past and present members of our research group for helpful discussions. This study was supported in part by grants from the Japan Biological Information Consortium (JBIC) affiliated with the New Energy and Industrial Technology Development Organization (M.I.) and the Ministry of Education, Science and Technology (Knowledge Cluster Initiative) (T.T. and M.I.).
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Keshavarz, P., Inoue, H., Sakamoto, Y. et al. No evidence for association of the ENPP1 (PC-1) K121Q variant with risk of type 2 diabetes in a Japanese population. J Hum Genet 51, 559–566 (2006). https://doi.org/10.1007/s10038-006-0399-0
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DOI: https://doi.org/10.1007/s10038-006-0399-0
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