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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

Leukotrienes
Type 2 Diabetes Mellitus
Genes
Leukotriene E4
Arachidonate 5-Lipoxygenase
Leukotriene B4
DNA
Introns
Population
Exons
Phenotype
Polymerase Chain Reaction
Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Microbiology (miscellaneous)
  • Cancer Research

Cite this

Postula, Marek ; Janicki, Piotr Kazimierz ; Rosiak, Marek ; Eyileten, Ceren ; Zaremba, Małgorzata ; Kaplon-Cieslicka, Agnieszka ; Sugino, Shigekazu ; Kosior, Dariusz Artur ; Opolski, Grzegorz ; Filipiak, Krzysztof Jerzy ; Mirowska-Guzel, Dagmara. / Targeted deep resequencing of ALOX5 and ALOX5APIN patients with diabetes and association of rare variants with leukotriene pathways. In: Experimental and Therapeutic Medicine. 2016 ; Vol. 12, No. 1. pp. 415-421.
@article{11b67a4ca85f4031a2ea1f304a627acd,
title = "Targeted deep resequencing of ALOX5 and ALOX5APIN patients with diabetes and association of rare variants with leukotriene pathways",
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.",
author = "Marek Postula and Janicki, {Piotr Kazimierz} and Marek Rosiak and Ceren Eyileten and Małgorzata Zaremba and Agnieszka Kaplon-Cieslicka and Shigekazu Sugino and Kosior, {Dariusz Artur} and Grzegorz Opolski and Filipiak, {Krzysztof Jerzy} and Dagmara Mirowska-Guzel",
year = "2016",
month = "7",
doi = "10.3892/etm.2016.3334",
language = "English (US)",
volume = "12",
pages = "415--421",
journal = "Experimental and Therapeutic Medicine",
issn = "1792-0981",
publisher = "Spandidos Publications",
number = "1",

}

Postula, M, Janicki, PK, Rosiak, M, Eyileten, C, Zaremba, M, Kaplon-Cieslicka, A, Sugino, S, Kosior, DA, Opolski, G, Filipiak, KJ & 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, vol. 12, no. 1, pp. 415-421. https://doi.org/10.3892/etm.2016.3334

Targeted deep resequencing of ALOX5 and ALOX5APIN patients with diabetes and association of rare variants with leukotriene pathways. / Postula, Marek; Janicki, Piotr Kazimierz; Rosiak, Marek; Eyileten, Ceren; Zaremba, Małgorzata; Kaplon-Cieslicka, Agnieszka; Sugino, Shigekazu; Kosior, Dariusz Artur; Opolski, Grzegorz; Filipiak, Krzysztof Jerzy; Mirowska-Guzel, Dagmara.

In: Experimental and Therapeutic Medicine, Vol. 12, No. 1, 07.2016, p. 415-421.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Targeted deep resequencing of ALOX5 and ALOX5APIN patients with diabetes and association of rare variants with leukotriene pathways

AU - Postula, Marek

AU - Janicki, Piotr Kazimierz

AU - Rosiak, Marek

AU - Eyileten, Ceren

AU - Zaremba, Małgorzata

AU - Kaplon-Cieslicka, Agnieszka

AU - Sugino, Shigekazu

AU - Kosior, Dariusz Artur

AU - Opolski, Grzegorz

AU - Filipiak, Krzysztof Jerzy

AU - Mirowska-Guzel, Dagmara

PY - 2016/7

Y1 - 2016/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84968831225&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84968831225&partnerID=8YFLogxK

U2 - 10.3892/etm.2016.3334

DO - 10.3892/etm.2016.3334

M3 - Article

C2 - 27347071

AN - SCOPUS:84968831225

VL - 12

SP - 415

EP - 421

JO - Experimental and Therapeutic Medicine

JF - Experimental and Therapeutic Medicine

SN - 1792-0981

IS - 1

ER -