Novel Interactions of Myristic Acid and FADS3 Variants Predict Atopic Dermatitis among Indonesian Infants.

Fatty acids exert a range of different biological activities that could be relevant in the development of atopic dermatitis (AD). This study investigated the association of glycerophospholipid fatty acids (GPL-FA) with AD, and their interactions with single nucleotide polymorphisms (SNP) of the FADS1-3 gene cluster. Among 390 infants of the Indonesian ISADI study, GPL-FA were measured in umbilical plasma (P-0y) and in buccal cells at birth (B-0y), and again in buccal cells at AD onset or one year (B-1y). Prospective and cross-sectional associations with AD were assessed by logistic regression. Interactions of GPL-FA with 14 SNP were tested assuming an additive model. AD was diagnosed in 15.4% of participants. In B-1y, C18:2n-6 was inversely associated with AD; and positive associations were observed for C18:1n-9, C20:4n-6, C22:6n-3 and C20:4n-6/C18:2n-6. There were no prospective associations with AD, however, a significant interaction between the SNP rs174449 and B-0y C14:0 (myristic acid) was observed. This study indicates that Indonesian infants with AD have increased rates of endogenous long-chain polyunsaturated fatty acid production, as well as higher C18:1n-9 levels. GPL-FA measured at birth do not predict later AD incidence; however, genotype interactions reveal novel effects of myristic acid, which are modified by a FADS3 variant.

Effects of probiotics on immunity and iron homeostasis: A mini-review.

Iron deficiency remains a major problem in both developed and developing countries. Iron supplementation has been used as a standard intervention for the prevention and treatment of iron deficiency anemia (IDA). There are many factors affecting the efficacy, including stunting, infections or inflammations, and genetics. Recently, some studies have been conducted to further investigate the effects of probiotics on immunity and iron homeostasis. This mini review discusses about some important factors that can improve the management of IDA.

Catastrophic results due to unrecognizing of congenital insensitivity to pain with anhidrosis in children with multiple long bones fractures: A case report of 27 years follow-up of two siblings.

INTRODUCTION: Congenital insensitivity to pain with anhidrosis (CIPA; OMIM 256,800) is a rare autosomal recessive disease. Although the clinical symptoms are known, the consensus of CIPA treatment has not been recognized. This is the first report of CIPA in Indonesia, a case of two siblings, male and female, whom we followed-up for 27 years. PRESENTATION OF CASE: After a series of multiple fractures from an early age, both patients who lived wheelchair-bound with their parents had been suffering from a recurrent debilitating infection on their lower extremities. The male patient eventually died from sepsis due to bronchopneumonia, years after the nonunion of both legs. The female patient underwent double above knee amputation. DISCUSSION: Observation showed that fracture in joint and metaphysis treated with open reduction ultimately end in disastrous outcomes like infection and non-union. On the contrary, the diaphyseal fracture has a better expectation to unite with casting immobilization. CONCLUSION: Unrecognizing of the clinical pictures of CIPA and minimal literature references in the past, misleads to late diagnosis and management. Genetic evaluation should be done for infants with unknown causes of high fever, anhidrosis combined with insensitivity to pain. Surgical intervention of metaphyseal fractures should be avoided due to tendencies of implants loosening, metal failures, recurrent infections followed with non-union, and instability.

Should formula for infants provide arachidonic acid along with DHA? A position paper of the European Academy of Paediatrics and the Child Health Foundation.

Recently adopted regulatory standards on infant and follow-on formula for the European Union stipulate that from February 2020 onwards, all such products marketed in the European Union must contain 20-50 mg omega-3 DHA (22:6n-3) per 100 kcal, which is equivalent to about 0.5-1% of fatty acids (FAs) and thus higher than typically found in human milk and current infant formula products, without the need to also include ω-6 arachidonic acid (AA; 20:4n-6). This novel concept of infant formula composition has given rise to concern and controversy because there is no accountable evidence on its suitability and safety in healthy infants. Therefore, international experts in the field of infant nutrition were invited to review the state of scientific research on DHA and AA, and to discuss the questions arising from the new European regulatory standards. Based on the available information, we recommend that infant and follow-on formula should provide both DHA and AA. The DHA should equal at least the mean content in human milk globally (0.3% of FAs) but preferably reach 0.5% of FAs. Although optimal AA intake amounts remain to be defined, we strongly recommend that AA should be provided along with DHA. At amounts of DHA in infant formula up to ∼0.64%, AA contents should at least equal the DHA contents. Further well-designed clinical studies should evaluate the optimal intakes of DHA and AA in infants at different ages based on relevant outcomes.

FADS1 and FADS2 Polymorphisms Modulate Fatty Acid Metabolism and Dietary Impact on Health.

Variants in the FADS gene cluster modify the activity of polyunsaturated fatty acid (PUFA) desaturation and the lipid composition in human blood and tissue. FADS variants have been associated with plasma lipid concentrations, risk of cardiovascular diseases, overweight, eczema, pregnancy outcomes, and cognitive function. Studies on variations in the FADS genecluster provided some of the first examples for marked gene-diet interactions in modulating complex phenotypes, such as eczema, asthma, and cognition. Genotype distribution differs markedly among ethnicities, apparently reflecting an evolutionary advantage of genotypes enabling active long-chain PUFA synthesis when the introduction of agriculture provided diets rich in linoleic acid but with little arachidonic and eicosapentaenoic acids. Discovering differential effects of PUFA supply that depend on variation of FADS genotypes could open new opportunities for developing precision nutrition strategies based either on an individual's genotype or on genotype distributions in specific populations.

The association of fatty acid desaturase gene polymorphisms on long-chain polyunsaturated fatty acid composition in Indonesian infants.

Background: Adequate availability of long-chain polyunsaturated fatty acids (LC-PUFAs) is important for human health from pregnancy to adulthood. Previous studies on fatty acid desaturase (FADS) gene single-nucleotide polymorphisms (SNPs) have been performed predominantly in Western populations and showed that FADS SNPs had a marked impact on LC-PUFA composition in blood and tissues. Objectives: We aimed to investigate the influence of fetal FADS genotypes on LC-PUFA composition in umbilical artery plasma lipids in Indonesian infants. Design: We performed a cross-sectional study to assess for these associations. Results: A total of 12 cord plasma n-6 (ω-6) and n-3 (ω-3) fatty acids were analyzed for associations with 18 FADS gene cluster SNPs from 390 women with single parturition from the Indonesian Prospective Study of Atopic Dermatitis in Infants (ISADI). Fetal FADS genotypes influenced cord plasma LC-PUFA composition, but, in contrast to previous studies from Western populations, the quantitatively predominant SNPs were associated with lower LC-PUFA content. Conclusion: To our knowledge, this study was the first in South East Asia on FADS genotypes and arterial cord blood fatty acids to show an association between fetal LC-PUFA composition and fetal FADS SNPs. The FADS genotype distribution differs markedly between different geographical populations. This trial was registered at clinicaltrials.gov as NCT02401178.

Study protocol to investigate the environmental and genetic aetiology of atopic dermatitis: the Indonesian Prospective Study of Atopic Dermatitis in Infants (ISADI).

INTRODUCTION: Atopic dermatitis (AD) is the most common skin disorder in young children worldwide, with a high impact on morbidity and quality of life. To date, no prospective study has been published on the incidence and potential predictors of AD in South East Asian populations. The Indonesian Prospective Study of Atopic Dermatitis in Infants (ISADI) will address the genetic, metabolic and dietary characteristics of mothers and their offspring, as well as potential determinants of AD within the first year of infant life. METHODS AND ANALYSIS: This prospective study will be undertaken in about 400 infants to investigate the direct and indirect effects of filaggrin (FLG) gene mutations, the genetic variants of FADS1, FADS2 and FADS3 and the role of long-chain polyunsaturated fatty acids (LCPUFA) on the development of AD. We will use standardised protocols for subject recruitment, umbilical artery plasma analysis, buccal cell sampling for genotyping, fatty acid analysis, physical exams, 3-day food-intake recall of mothers and children, as well as comprehensive questionnaires on environmental, socioeconomic and AD-related factors, including family history. Monthly monitoring by telephone and physical exams every 3 months will be carried out to assess participants' anthropometry, medical history and incidence of AD diagnosis during the first year of life. Hypotheses-driven analyses of quality-controlled dietary, genetic and metabolic data will be performed with state-of-the-art statistical methods (eg, AD-event history, haplotype, dietary or metabolic factor analysis). Direct and indirect effects of genetics and LCPUFA in buccal cell and cord plasma glycerophospholipids as potential mediators of inflammation on AD development will be evaluated by path analysis. ETHICS AND DISSEMINATION: The Permanent Medical Research Ethics Committee in Medicine and Health/Faculty of Medicine Universitas Indonesia/Dr Cipto Mangunkusumo Hospital (No. 47/H2.F1/ETIK/2014) approved the study protocol (extended by the letter no. 148/UN2.F1/ETIK/2015). We aim to disseminate our findings via publication in an international journal with high impact factor.