Targeted deep resequencing of ALOX5 and ALOX5APIN patients with diabetes and association of rare variants with leukotriene pathways

Marek Postula, Piotr Kazimierz Janicki, Marek Rosiak, Ceren Eyileten, Małgorzata Zaremba, Agnieszka Kaplon-Cieslicka, Shigekazu Sugino, Dariusz Artur Kosior, Grzegorz Opolski, Krzysztof Jerzy Filipiak, Dagmara Mirowska-Guzel

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Abstract

The aim of the present study was to investigate a possible association between the accumulation of rare coding variants in the genes for arachidonate 5-lipoxygenase (ALOX5) and ALOX5-activating protein (ALOX5AP), and corresponding production of leukotrienes (LTs) in patients with type 2 diabetes mellitus (T2DM) receiving acetylsalicylic therapy. Twenty exons and corresponding introns of the selected genes were resequenced in 303 DNA samples from patients with T2DM using pooled polymerase chain reaction amplification and next-generation sequencing, using an Illumina HiSeq 2000 sequencing system. The observed non-synonymous variants were further confirmed by individual genotyping of DNA samples comprising of all individuals from the original discovery pools. The association between the investigated phenotypes was based on LTB4 and LTE4 concentrations, and the accumulation of rare missense variants (genetic burden) in investigated genes was evaluated using statistical collapsing tests. A total of 10 exonic variants were identified for each resequenced gene, including 5 missense and 5 synonymous variants. The rare missense variants did not exhibit statistically significant differences in the accumulation pattern between the patients with low and high LTs concentrations. As the present study only included patients with T2DM, it is unclear whether the absence of observed association between the accumulation of rare missense variants in investigated genes and LT production is associated with diabetic populations only or may also be applied to other populations.

Original languageEnglish (US)
Pages (from-to)415-421
Number of pages7
JournalExperimental and Therapeutic Medicine
Volume12
Issue number1
DOIs
StatePublished - Jul 2016

All Science Journal Classification (ASJC) codes

  • Immunology and Microbiology (miscellaneous)
  • Cancer Research

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    Postula, M., Janicki, P. K., Rosiak, M., Eyileten, C., Zaremba, M., Kaplon-Cieslicka, A., Sugino, S., Kosior, D. A., Opolski, G., Filipiak, K. J., & Mirowska-Guzel, D. (2016). Targeted deep resequencing of ALOX5 and ALOX5APIN patients with diabetes and association of rare variants with leukotriene pathways. Experimental and Therapeutic Medicine, 12(1), 415-421. https://doi.org/10.3892/etm.2016.3334