title: Evaluation of the ENPP1 and PLIN single nucleotide polymorphisms with type 2 diabetes in a Taiwanese population: evidence for replication and gene-gene interaction.
abstract: 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.
authors.affiliation: Department of Hepatogastroenterology, Tainan Municipal Hospital, Tainan, Taiwan.
authors.forename: Chun-Hsiang
authors.initials: CH
authors.lastname: Wang
authors.forename: Wan-Sheng
authors.initials: WS
authors.lastname: Ke
authors.forename: Eugene
authors.initials: E
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D042522:DNA Replication Timing / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics*; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011755:Pyrophosphatases / Q000235:genetics*; D013624:Taiwan / Q000453:epidemiology
chemical_list: D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases