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Evaluation of the ENPP1 and PLIN Single Nucleotide Polymorphisms With Type 2 Diabetes in a Taiwanese Population
  1. Chun-Hsiang Wang, MD*,
  2. Wan-Sheng Ke, MD,
  3. Eugene Lin, PhD‡§
  1. From the *Department of Hepatogastroenterology, Tainan Municipal Hospital, Tainan, Taiwan, †Department of Internal Medicine, Kuang Tien General Hospital, Taichung County, Taiwan, ‡Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, and §Vita Genomics, Inc, Wugu Shiang, Taipei, Taiwan.
  1. Received December 19, 2011, and in revised form May 16, 2012.
  2. Accepted for publication September 12, 2012.
  3. Reprints: Eugene Lin, PhD, Vita Genomics, Inc, 7 Fl, No. 6, Sec. 1, Jung-Shing Road, Wugu Shiang, Taipei, Taiwan. E-mail: eugene.lin{at}
  4. Supported by Vita Genomics, Inc and SBIR grants from the Department of Economic Affairs in Taiwan for funding this research.
  5. Wang and Ke contributed equally to this work.
  6. The authors have no conflicts of interest that are directly relevant to the content of this study.

Evidence for Replication and Gene-Gene Interaction


Background Addressing gene-gene interactions is essential in defining a trait implicating complex disease-related mechanisms. In this study, we aimed to explore both main effects of single-locus and multi-locus interactions to test the hypothesis that the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) and perilipin (PLIN) genes may contribute to the etiology of type 2 diabetes (T2D) independently and/or through complex interactions in a Taiwanese population.

Methods There were 416 patients with a diagnosis of T2D and 188 age- and sex-similar control subjects. To investigate gene-gene interactions, we used both the generalized multifactor dimensionality reduction method and logistic regression models.

Results Allelic and genotypic analyses showed significant main effects of ENPP1 rs1044498 (P = 0.000005 and 0.00007, respectively) on the risk of T2D after Bonferroni correction (P < 0.05/2 = 0.025). Compared to the carrier of the AA genotype of the ENPP1 rs1044498 polymorphism, the likelihood of T2D was 2.442 (95% confidence interval, 1.592–3.747) for the carrier of combined AC+CC genotypes after adjustment of sex and body mass index. In addition, the carriers of AA variant in the PLIN rs894160 polymorphism had a higher risk to T2D than those with the combined AG+GG variants (adjusted odds ratio, 1.856; 95% confidence interval, 1.106–3.115) after adjustment of sex and body mass index. Furthermore, the significant 2-locus (P = 0.001) generalized multifactor dimensionality reduction model was identified between ENPP1 and PLIN. Analyses using logistic regression models confirmed the gene-gene interaction.

Conclusions The results suggest that the ENPP1 and PLIN genes may contribute to the risk of T2D independently and/or in an interactive manner in a Taiwanese population.

Key Words
  • gene-gene interactions
  • single nucleotide polymorphisms
  • type 2 diabetes
  • T2D susceptibility gene

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