A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE

Quintana, Luís F.; Guzmán, Blanca; Collado, Sílvia; Clària, Joan; Poch, Esteban

doi:10.1038/sj.ki.5000147

Cited by 39 publications

(26 citation statements)

References 24 publications

(32 reference statements)

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“…as shown in table ii, the frequencies of the variants identified in the Indian population (present study) were compared to the frequencies reported in caucasians (42,43), Blacks (42), chinese (40), Koreans (44), Brazilians (45) and Spanish (27). the frequencies appeared to vary in the various populations.…”

Section: Resultsmentioning

confidence: 99%

“…One recent publication also reported the association of alOx12 with the onset of natural menopause in caucasian females (54), indicating a role for alOx12 in hormone-related events in females. the alOx12 polymorphism has been shown to be associated with diseases, including hypertension, diabetic nephropathy and colorectal cancer (27). however, little information exists on the association of the alOx12 polymorphism with other types of cancers.…”

Section: Discussionmentioning

confidence: 99%

“…as the polymorphism alters the amino acid from glutamine to arginine, it is likely to alter the enzyme kinetics which may affect the levels of the alOx12 metabolites (40,56,57). hypertensive patients with GG homozygous variants were found to have higher amounts of urinary 12-hEtE when compared to patients with either the aa or aG variant (27). as 12-hEtE and other metabolites are implicated in various processes, including cell proliferation, adhesion and invasiveness of cancer cells (1,58-62), anomalies in the generation of these metabolites are likely to play a role in the development of cancer, its growth and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…hence, any imbalance in eicosanoids may lead to abnormal generation of ROS, inflammation and the development of cancer (19)(20)(21)(22). Several lines of evidence have implicated alOxs and their products in various pathologies linked with inflammation, including Alzheimer's disease (23,24), atherosclerosis (25,26), hypertension (27), stroke (27)(28)(29) and cancer (7). Evidence links up-regulated alOx12 expression to the development of cancer, sustenance, growth and metastasis (11,(30)(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

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Association of a functional polymorphism (Gln261Arg) in 12-lipoxygenase with breast cancer

Prasad

Kolli

Moganti

2011

Experimental and Therapeutic Medicine

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Abstract. the overexpression of arachidonyl lipoxygenase-12 (alOx12) in breast cancer has been reported. hence, we examined whether a non-synonymous polymorphism of alOx12 (mrna, a835G; Gln261arg) is associated with breast cancer in females. the polymorphism was detected in genomic dna by pcr-rFlp. the association between the a835G polymorphism and breast cancer risk was measured by odds ratio (OR) with 95% confidence intervals (CIs) using Fisher's exact test, and differences were considered significant at p<0.05. the frequencies of aa (wild-type), GG (homozygous variant) and aG (heterozygous variant) were 59.5, 0.9 and 39.6% in the controls, and 39.3, 2.5 and 58.2% in the breast cancer cases, respectively. the frequency of the aG genotype was higher in the patients compared to the controls (p<0.0014). the frequency of the GG variant was 2.5 and 0.9% in the cancer subjects and controls, respectively. the relative risk of breast cancer was 2 times greater (Or=2.227) at 95% ci when compared to the relative risk of the heterozygous variant. For the GG genotype, the risk was 4 times greater (Or=4.125) at 95% ci than that of the controls, suggesting a positive association of the aG genotype with the occurrence of breast cancer. the frequencies of the polymorphism were different in different populations. the arg/Gln and arg/arg variants were associated with an increased risk of breast cancer, and the frequencies of the variants differed considerably among various populations. The identification of a gene with links to breast cancer may impact screening, diagnosis and drug development.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of a functional polymorphism (Gln261Arg) in 12-lipoxygenase with breast cancer

Prasad

Kolli

Moganti

2011

Experimental and Therapeutic Medicine

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“…In a study of 200 patients with essential hypertension (aged 56  1 years, mean  s.e.m., including 97 males) and 166 matched controls (aged 54  1 years, 91 males), Quintana et al, [42] found that a non-synonymous polymorphism in ALOX12 is associated with both essential hypertension and urinary levels of 12(S)-HETE.…”

Section: Chromosome 10mentioning

confidence: 99%

Analysis of candidate genes of QTL and chromosomal regions for essential hypertension in the rat model

Wang

Zhu²,

Huang

et al. 2012

OJGen

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This is an in silico analysis of quantitative trait loci (QTLs), genes, polymorphisms, and chromosomal regions regulating hypertension in the rat genome. Utilizing PGmapper, a program that matches phenoltypes to genes, we identified 266 essential hypertension-associated genes (HyperA), and 83 of these genes contain known hypertension-associated polymorphisms (HyperAP). The majority of HyperAP have been reported in recent years. Surprisingly, only a few of these HyperAP genes have been investigated for their candidacy as the QTL for hypertension. The frequency of candidate genes within peak regions of the QTL is higher than the rest of the QTL region. We also found that QTL located in both gene-rich regions and gene-rich chromosomes contained the most candidate genes. However, the number of candidate genes within a peak region is not associated with the number of total genes in a QTL region. This data could not only facilitate a more rapid and comprehensive identification for the causal genes underlying hypertension in rats, but also provides new insights into genomic structure in regulation of hypertension.

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Lipoxygenase Dynamics and Catalysis Studied by Temperature‐Dependent Hydrogen–Deuterium Exchange

Offenbacher,

Guy

2024

Encyclopedia of Inorganic and Bioinorganic Chemistry

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An active pursuit in biochemistry is the understanding of how the structure and dynamics of protein systems regulate their biological function. In this chapter, we describe temperature‐dependent hydrogen–deuterium exchange mass‐spectrometry (TDHDX‐MS) as a tool used to investigate the structure and dynamics of metalloenzymes in solution. While the method is applicable to many metalloproteins, this review will present TDHDX‐MS studies centered on the widely represented family of mononuclear, non‐heme iron containing lipoxygenase (LOX) enzymes that oxidize fatty acids to initiate biological reactions and activate cellular signaling. We will present how TDHDX has been used to describe the anisotropic nature of energy transfer in LOXs to initiate the rate‐limiting hydrogen atom transfer reaction that proceeds through a tunneling process. Further, TDHDX‐MS has been used detect protein motions and conformations in LOXs related to molecular recognition, protein allostery, and polymorphisms linked to disease.

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A coding polymorphism in the 12-lipoxygenase gene is associated to essential hypertension and urinary 12(S)-HETE

Cited by 39 publications

References 24 publications

Association of a functional polymorphism (Gln261Arg) in 12-lipoxygenase with breast cancer

Association of a functional polymorphism (Gln261Arg) in 12-lipoxygenase with breast cancer

Analysis of candidate genes of QTL and chromosomal regions for essential hypertension in the rat model

Lipoxygenase Dynamics and Catalysis Studied by Temperature‐Dependent Hydrogen–Deuterium Exchange

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