Abstract
BackgroundIt is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children.MethodsAE (n=20) and non-AE (n=104) children participating in the Sabadell cohort within the INfancia y Medio Ambiente (INMA) Project were included in the present study. RT-PCR with TaqMan Low-Density Array cards was used to measure the mRNA-expression of FADS1, FADS2 and ELOVL5. LC-PUFA levels were measured by fast gas chromatography in plasma phospholipids. The relationship of gene expression with LC-PUFA levels and enzyme activities was evaluated by Pearson’s rank correlation coefficient, and logistic regression models were used to study its association with risk of developing AE.ResultsChildren with AE had lower levels of several n-6 PUFA members, dihomo-γ-linolenic (DGLA) and arachidonic (AA) acids. mRNA-expression levels of FADS1 and 2 strongly correlated with DGLA levels and with D6D activity. FADS2 and ELOVL5 mRNA-expression levels were significantly lower in AE than in non-AE children (-40.30% and -20.36%; respectively), but no differences were found for FADS1.Conclusions and SignificanceChanges in the mRNA-expression levels of FADS1 and 2 directly affect blood DGLA levels and D6D activity. This study suggests that lower mRNA-expressions of FADS2 and ELOVL5 are associated with higher risk of atopic eczema in young children.
Highlights
Atopic eczema (AE) is a multifactorial skin disease occurring most frequently in early childhood
DGLA and AA levels were significantly lower in atopic eczema (AE) children than in controls (p= 0.014 and p= 0.046, respectively) (Table 1)
It is known that the skin is the target organ in patients with atopic eczema; previous studies suggested that the GLA, DGLA and AA present in epidermal phospholipids are biosynthesized endogenously elsewhere and transported by the bloodstream to the epidermis, where phospholipid etherification takes place
Summary
Atopic eczema (AE) is a multifactorial skin disease occurring most frequently in early childhood. It is caused by a complex interplay between immunological, genetics, biochemical, psychological and environmental factors. DGLA can be converted into AA by Δ5-desaturase (D5D, encoded by the FADS1 gene) (summarized in Figure 1) [9,10,11,12,13] It is unknown if changes in the gene expression of the desaturase and elongase enzymes are associated with abnormal n-6 long chain polyunsaturated fatty acid (LC-PUFA) levels in children with atopic eczema (AE). We analyzed whether mRNA-expression of genes encoding key enzymes of LC-PUFA synthesis (FADS1, FADS2 and ELOVL5) is associated with circulating LC-PUFA levels and risk of AE in 4-year-old children
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