Biosynthesis of leukotriene B4 in human polymorphonuclear leukocytes: regulation by cholesterol and other lipids

Zagryagskaya, Anna N.; Aleksandrov, Dmitry; Pushkareva, Marina A.; Galkina, Svetlana I.; Grishina, Zoryana V.; Sud’ina, Galina F.

doi:10.1080/15476910802482888

Cited by 10 publications

(5 citation statements)

References 45 publications

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“…Evidence suggests that the rare T allele of rs17525495 increases LTA4H gene transcription [37], while the rare alleles of rs6538697, rs2660898, and rs1978331 are associated with lower LTB4 levels [13], which is comparable to the present study findings. Some studies have shown that LTB4 biosynthesis is regulated by cholesterol [38], and inhibition of Leukotriene may reduce plasma TG levels [39]. Our data also showed high correlation of LTB4 levels with TC, TG, and LDL-cholesterol, after adjusting for age, gender, and statins.…”

Section: Discussionsupporting

confidence: 73%

Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians

Nair

Shanker

Arvind

et al. 2013

ISRN Vascular Medicine

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Leukotrienes are potent inflammatory and lipid mediators that participate in atherosclerosis. We analyzed the association of Leukotriene gene (ALOX5, ALOX5AP, LTA4H, and LTC4S) polymorphisms and plasma Leukotriene B4 (LTB4) levels with coronary artery disease (CAD) in a representative cohort of Asian Indians. In all, 136 functional single nucleotide polymorphisms (SNPs) were selected using in silico tools. Forty-five polymorphic SNPs were ranked for predicted functional effect using FastSNP. Finally, 14 functional SNPs along with 10 SNPs identified from the literature were genotyped in 340 CAD patients and 340 controls. Plasma LTB4 levels were measured in 150 cases and 150 controls. None of the 24 SNPs showed significant association with CAD. Plasma LTB4 levels were higher in cases than in controls (76.42 ± 4.46 pg/mL versus 60.89 ± 2.61 pg/mL) ( = 0.003), with greater risk being associated with the top quartile as compared to the bottom quartile after adjusting for potential confounders (OR 8.94, 95% CI 2.56-31.95; = 0.001). Four SNPs in the LTA4H gene showed significant association with LTB4 levels ( < 0.05) of which rs1978331 ( = 0.035) remained significant after correction for multiple testing. LTB4 showed strong correlation with lipids ( = 0.24-34) only in cases. Our pilot study suggests that the association between Leukotrienes gene polymorphisms and CAD risk may be modulated through plasma LTB4 levels.

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Section: Discussionsupporting

confidence: 73%

Association of Leukotriene Gene Variants and Plasma LTB4 Levels with Coronary Artery Disease in Asian Indians

Nair

Shanker

Arvind

et al. 2013

ISRN Vascular Medicine

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“…Mgst2 encodes microsomal glutathione S-transferase, an enzyme involved in synthesis of leukotrienes (LT) via the 5-lipoxygenase (5-LO) pathway. Synthesis of LT through this pathway has been shown to be inhibited by cholesterol (Zagryagskaya et al 2008). Foxo1 encodes forkhead box transcription factor O1 (FoxO1), a key regulator in bile acid biosynthesis and hence likely to affect subsequent catabolism of cholesterol (Li et al 2009).…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Genetic Mapping Using the Mouse Diversity Outbred Population

et al. 2012

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The JAX Diversity Outbred population is a new mouse resource derived from partially inbred Collaborative Cross strains and maintained by randomized outcrossing. As such, it segregates the same allelic variants as the Collaborative Cross but embeds these in a distinct population architecture in which each animal has a high degree of heterozygosity and carries a unique combination of alleles. Phenotypic diversity is striking and often divergent from phenotypes seen in the founder strains of the Collaborative Cross. Allele frequencies and recombination density in early generations of Diversity Outbred mice are consistent with expectations based on simulations of the mating design. We describe analytical methods for genetic mapping using this resource and demonstrate the power and high mapping resolution achieved with this population by mapping a serum cholesterol trait to a 2-Mb region on chromosome 3 containing only 11 genes. Analysis of the estimated allele effects in conjunction with complete genome sequence data of the founder strains reduced the pool of candidate polymorphisms to seven SNPs, five of which are located in an intergenic region upstream of the Foxo1 gene.

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“…Therefore, IH-induced hyperlipidemia could also contribute to IH-associated atherogenesis (10). Of note, the biosynthesis of LTB4 is regulated by cholesterol (54) and inhibition of leukotriene may reduce plasma triglyceride (TG) levels (55). However, it remains unclear whether IH-induced hyperlipidemia affects the biosynthesis of LTB4 and downstream atherogenesis.…”

Section: Discussionmentioning

confidence: 99%