Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population

Maycotte-Cervantes, María Luisa; Aguilar-Galarza, Adriana; Anaya‐Loyola, Miriam Aracely; Anzures-Cortés, Ma. de Lourdes; Haddad-Talancón, Lorenza; Méndez-Rangel, Akram Sharim; García-Gasca, Teresa; Rodríguez-García, Víctor Manuel; Moreno-Celis, Ulisses

doi:10.3390/nu12113389

Cited by 7 publications

(8 citation statements)

References 34 publications

(34 reference statements)

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“…This method precludes the The mechanism for changes in sebum might be related to the alterations in genes responsible for lipids metabolism, 33 and our results also revealed that the genes related to lipid synthesis and metabolism (e.g., FASN, SCD5, FADS1, FADS2, and ELOVLs) were down-regulated in the non-lesional skin of AD and significantly associated with the skin inflammations and barrier features of AD. These genes have been shown to be intimately involved in TG synthesis, [34][35][36][37] so the downregulation of their expression is consistent with our observation of a significant decrease in TG in the skin of AD patients. Analysis of single-cell RNA-sequence data revealed that these dysregulated genes were mainly de-…”

Section: Discussionsupporting

confidence: 91%

Dysregulated lipidome of sebum in patients with atopic dermatitis

Yin

Qiu

Zhu

et al. 2022

Allergy

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Background: Lipids are the major components of skin barrier, mainly produced by keratinocytes and sebaceous glands. Previous studies on barrier dysfunction of atopic dermatitis (AD) mainly focus on the lipids from keratinocytes, whereas the role of sebaceous gland-derived lipids in AD has long been underrecognized. Methods:The sebum secreted on the skin surface of AD patients was measured using the Delfin Sebum Scale. Sebum was collected using Sebutape patches and subjected for liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis.Multivariate data analysis was applied to explore the relationship among the lipidome, clinical features, and sebaceous gland-related molecules. Results:The amount of sebum secreted from sebaceous glands was decreased in AD patients and was negatively correlated with the barrier function and disease severity. LC-MS/MS revealed the lipidome of sebum, which clustered distinctly between AD patients and healthy individuals. Among the differential lipid subclasses, triglycerides (TG) were exclusively decreased in AD patients and correlated with disease severity.The first principal component scores of AD patients, which represented the main signature of the lipidome, were positively correlated with the SCORAD scores and were significantly different across the patient groups with differential clinical symptoms such as skin dryness and pruritus. Further analysis on the previously published transcriptome data revealed aberrant expression of lipid metabolism-related genes in non-lesional skin of AD patients, which was associated with skin inflammation and barrier dysfunction and mainly derived from inner root sheath keratinocytes and sebaceous gland cells.

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Section: Discussionsupporting

confidence: 91%

Dysregulated lipidome of sebum in patients with atopic dermatitis

Yin

Qiu

Zhu

et al. 2022

Allergy

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“…Multiple studies reported that obesity is related to several factors, including elevated energy consumption, a sedentary lifestyle, the consumption of alcoholic beverages, smoking, and several genetic factors [ 5 ]. For example, studies have described the positive or negative effects of single nucleotide polymorphisms (SNPs) on metabolic pathways and health conditions [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity

Cadena-López

Hernández-Rodríguez

Aguilar-Galarza

et al. 2022

Genes

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Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Therefore, the present work focused on determining the association between anthropometric markers and biochemical and dietary factors related to obesity and SNPs of leptin pathway genes, such as the leptin gene (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), and the melanocortin 4 receptor (MC4R). A population of 574 young Mexican adults of both sexes, aged 19 years old on average and without metabolic disorders previously diagnosed, underwent a complete medical and nutritional evaluation, biochemical determination, and DNA extraction from the blood; DNA samples were subsequently genotyped. Association analyses between anthropometric, biochemical, and dietary variables with SNPs were performed using binary logistic regressions (p-value = 0.05). Although the sampled population did not have previously diagnosed diseases, the evaluation results showed that 33% were overweight or obese according to BMI and 64% had non-clinically elevated levels of body fat. From the 74 SNP markers analyzed from the five previously mentioned genes, 62 showed polymorphisms within the sampled population, and only 35 of these had significant associations with clinical variables. The risk associations (OR > 1) occurred between clinical markers with elevated values for waist circumference, waist–height index, BMI, body fat percentage, glucose levels, insulin levels, HOMA-IR, triglyceride levels, cholesterol levels, LDL-c, low HDL-c, carbohydrate intake, and protein intake and SNPs of the LEP, LEPR, PCSK1, and MC4R genes. On the other hand, the protective associations (OR < 1) were associated with markers including elevated values for insulin, HOMA-IR, cholesterol, c-LDL, energy intake > 2440 Kcal/day, and lipid intake and SNPs of the LEP and LEPR genes and POMC. The present study describes associations between SNPs in leptin pathway genes, revealing positive and negative interactions between reported SNPs and the clinical markers related to obesity in a sampled Mexican population. Hence, our results open the door for the further study of new genetic variants and their influence on obesity.

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“…Results of studies conducted by Liu et al have suggested that DNA‐methylation may play an intermediary role rather than a causal role in the relationship between the ELOVL2 gene and clinical outcomes 25 . Moreover, three ELOVL2 genetic variants were found to be protective factors against high cholesterol and glucose, insulin resistance and high body fat content 27 . Other SNPs in ELOVL2 gene were associated with risk factors of cardiovascular diseases such as total‐ and LDL‐cholesterol, insulin and BMI 27 .…”

Section: Discussionmentioning

confidence: 99%

“…25 Moreover, three ELOVL2 genetic variants were found to be protective factors against high cholesterol and glucose, insulin resistance and high body fat content. 27 Other SNPs in ELOVL2 gene were associated with risk factors of cardiovascular diseases such as totaland LDL-cholesterol, insulin and BMI. 27 Therefore, hypermethylation of ELOVL2 gene in whole blood does not necessarily mirror a risk factor or a mechanism of disease.…”

Section: Discussionmentioning

confidence: 99%

ELOVL2‐methylation and renal and cardiovascular event in patients with chronic kidney disease

Obeid,

Rickens,

Heine

et al. 2023

Eur J Clin Investigation

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BackgroundMethylation of the Elongation Of Very Long Chain Fatty Acids‐Like 2 (ELOVL2) gene promoter may predict premature ageing and cardiovascular risk.MethodsWe studied the cross‐sectional associations between blood ELOVL2‐methylation and cardiovascular risk factors in 350 patients with chronic kidney disease (CKD) stage G2–G4 aged between 22 and 90 years. In a follow‐up study for a mean of 3.9 years, we investigated the association between baseline ELOVL2‐methylation and renal or cardiovascular events including death.ResultsELOVL2‐methylation at seven CpG cites increased with age (the correlation coefficients between 0.67 and 0.87, p < 0.001). The ELOVL2‐CpGs methylation was lower in patients with CKD stage G2 versus those in stage G3a, G3b and G4, but the differences were explained by age. ELOVL2‐CpGs methylation showed no correlations with cardiovascular risk factors after adjusting for age. During the follow‐up, 64 patients showed deterioration in renal function or died and 77 showed cardiovascular events or died. The hazard ratio and 95% confidence intervals for renal or cardiovascular events according to baseline ELOVL2‐CpGs methylation were not significant after adjustment for covariates.ConclusionsELOVL2‐hypermethylation showed a strong association with age, but was not independently associated with cardiovascular risk factors or with future renal or cardiovascular events in patients with CKD. ELOVL2 gene methylation is not likely to be itself a cause for ageing or illnesses, but it could be rather influenced by other upstream processes that deserve investigation.

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Influence of Single Nucleotide Polymorphisms of ELOVL on Biomarkers of Metabolic Alterations in the Mexican Population

Cited by 7 publications

References 34 publications

Dysregulated lipidome of sebum in patients with atopic dermatitis

Dysregulated lipidome of sebum in patients with atopic dermatitis

Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity

ELOVL2‐methylation and renal and cardiovascular event in patients with chronic kidney disease

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