Lifetime prevalence and determinants of hand eczema in an adolescent population in Germany: 15-year follow-up of the LISA cohort study.

BACKGROUND: Hand eczema is a common inflammatory skin disorder in both adolescence and adulthood. OBJECTIVES: We sought to assess the lifetime prevalence of hand eczema and associated exogenous and endogenous risk factors among adolescents in Germany. METHODS: This was a cross-sectional study embedded into a prospective population-based birth cohort in four regions of Germany, which recruited healthy neonates born between November 1997 and January 1999. We included 1736 participants who had completed the 15-year follow-up from birth cohort and 84.6% (1468/1736) had clearly reported whether they have ever had hand eczema. All the data were based on questionnaires and blood tests (immunoglobulin E). Multivariable logistic regression analysis was used to examine endogenous and exogenous factors in relation to the lifetime prevalence of hand eczema among adolescents. RESULTS: One thousand four hundred and sixty-eight adolescents (715 girls, 48.7%) were included in the final analysis. The lifetime prevalence of hand eczema among adolescents at the age of 15 was 10.4% (95% confidence interval [CI]: 8.9%-12.1%), with a significantly higher lifetime prevalence among girls than boys (12.7% vs. 8.2%, P = 0.005). Multivariable logistic regression analysis indicated statistically significant associations between the lifetime prevalence of hand eczema and having ever been diagnosed with atopic dermatitis (aOR = 1.8, 95% CI: 1.1-2.8) or having ever had dry skin (aOR = 1.9, 95% CI: 1.1-3.1), respectively. No statistically significant independent associations were found between asthma, hay fever, allergy-related clinical symptoms, immunoglobulin E positivity and other exogenous factors in relation to hand eczema. CONCLUSION: Our study fills a research gap on the epidemiological burden of hand eczema among adolescents. One out of ten ever suffered from hand eczema until age 15 years indicating that hand eczema constitutes a significant burden in paediatric populations. The role of atopic dermatitis in hand eczema reinforces previous findings. Exogenous risk factors warrant further investigation.

MAIT cell activation in adolescents is impacted by bile acid concentrations and body weight.

Bile acids (BAs) are produced by liver hepatocytes and were recently shown to exert functions additional to their well-known role in lipid digestion. As yet it is not known whether the mucosal-associated invariant T (MAIT) cells, which represent 10-15% of the hepatic T cell population, are affected by BAs. The focus of the present investigation was on the association of BA serum concentration with MAIT cell function and inflammatory parameters as well as on the relationship of these parameters to body weight. Blood samples from 41 normal weight and 41 overweight children of the Lifestyle Immune System Allergy (LISA) study were analyzed with respect to MAIT cell surface and activation markers [CD107a, CD137, CD69, interferon (IFN)-γ, tumor necrosis factor (TNF)-α] after Escherichia coli stimulation, mRNA expression of promyelocytic leukemia zinc finger protein (PLZF) and major histocompatibility complex class I-related gene protein (MR1), the inflammatory markers C-reactive protein (CRP), interleukin (IL)-8 and macrophage inflammatory protein (MIP)-1α as well as the concentrations of 13 conjugated and unconjugated BAs. Higher body weight was associated with reduced MAIT cell activation and expression of natural killer cell marker (NKp80) and chemokine receptor (CXCR3). BA concentrations were positively associated with the inflammatory parameters CRP, IL-8 and MIP-1α, but were negatively associated with the number of activated MAIT cells and the MAIT cell transcription factor PLZF. These relationships were exclusively found with conjugated BAs. BA-mediated inhibition of MAIT cell activation was confirmed in vitro. Thus, conjugated BAs have the capacity to modulate the balance between pro- and anti-inflammatory immune responses.

The sex-shift in single disease and multimorbid asthma and rhinitis during puberty - a study by MeDALL.

BACKGROUND: Cross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex-specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data. METHODS: In six European population-based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero-allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta-analysis. FINDINGS: We included data from 19 013 participants from birth to age 14-20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%-confidence interval 0.73-0.86) and 0.86 (0.79-0.94), respectively (sex-puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63-0.81 and 0.81, 0.64-1.02, respectively (sex-puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female-male-OR 0.55, 0.46-0.64) and a considerable shift towards a sex-balanced prevalence after puberty onset (0.89, 0.74-1.04); sex-puberty interaction: P < .001. INTERPRETATION: The male predominance in prevalence before puberty and the "sex-shift" towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently.

Maternal and fetal genetic contribution to gestational weight gain.

BACKGROUND: Clinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG. PARTICIPANTS AND METHODS: A genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10 543 mothers and 16 317 offspring of European origin, with replication in 10 660 mothers and 7561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (for example, maternal body mass index (BMI) and glucose, birth weight). RESULTS: Approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and the fetal genome made a surprisingly minor contribution to explain variation in GWG. Variants near the pregnancy-specific beta-1 glycoprotein 5 (PSG5) gene reached genome-wide significance (P=1.71 × 10-8) for total GWG in the offspring genome, but did not replicate. Some established variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birth weight variants were largely unrelated to GWG. CONCLUSIONS: We found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

Associations between fatty acids and low-grade inflammation in children from the LISAplus birth cohort study.

BACKGROUND/OBJECTIVES: Assessing fatty acid (FA) composition in relation to inflammatory markers can shed light on the role of different FA and their metabolism in low-grade inflammation. Existing exploratory studies in children are scarce, and findings inconsistent. We hence aim to analyse associations of FA with common inflammatory markers, high-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), in 10-year-old children. SUBJECTS/METHODS: Complete data were available for 958 participants from the 10-year follow-up of the LISAplus (Influence of Lifestyle-Related Factors on the Immune System and the Development of Allergies in Childhood plus the Influence of Traffic Emissions and Genetics) birth cohort study. FA composition was assessed in serum glycerophospholipids. Hs-CRP and IL-6 were categorised into three levels. Associations of FA with inflammatory markers were assessed using multinomial logistic regression, adjusting for potential confounders. Additionally, sex-stratified analyses were carried out. RESULTS: FA exposures associated with significantly higher low-grade inflammation, as indicated by higher hs-CRP or IL-6 levels, included: palmitic acid (PA) (IL-6: P<0.001, 95% confidence interval: 1.30; 2.43), arachidonic acid (AA) (hs-CRP: P=0.002, 1.07; 1.31), n-6 highly unsaturated FA (HUFA) (hs-CRP: P=0.002, 1.06; 1.27), ratio of AA to linoleic acid (AA/LA) (hs-CRP: P<0.001, 1.16; 1.62) and total saturated FA (SFA) (IL-6: P<0.001, 1.77; 3.15). FA exposures associated with reduced levels of inflammatory markers included LA (hs-CRP: P=0.001, 0.84; 0.96; IL-6: P<0.001, 0.69; 0.90) and total polyunsaturated FA (PUFA) (IL-6: P<0.001, 0.57; 0.78). CONCLUSIONS: These findings suggest that higher SFA and minor n-6 HUFA, namely PA and AA, are associated with increased low-grade inflammation in children, whereas the major dietary n-6 PUFA and total PUFA are associated with reduced inflammation. Elevated desaturase activity, estimated by the ratio AA/LA, may be associated with higher inflammation, particularly in boys.

Early life travelling does not increase risk of atopic outcomes until 15 years: results from GINIplus and LISAplus.

BACKGROUND: Westernized lifestyle has been blamed for allergy epidemics. One of its characteristics is increased distances and frequency of travelling from early life onwards. Early life travelling to places which substantially differ from home environment in terms of climate, vegetation and food could increase the exposure to further unknown allergens and hence promote the development of allergies, but no epidemiological study has investigated this speculation. METHODS: Detailed data on travelling during the first 2 years of life as well as a range of atopic outcomes along with potential confounders up to age 15 years were collected prospectively within two large population-based multicentre German birth cohorts - GINIplus and LISAplus. Farthest travelling destination (within Germany; middle/northern/eastern Europe; southern Europe; outside Europe), total number of trips and their combination were considered as exposures. Six atopic outcomes were used: (1) doctor-diagnosed asthma, (2) doctor-diagnosed allergic rhinitis, (3) nose and eye symptoms, (4) sensitization to food allergens, (5) sensitization to indoor and (6) outdoor inhalant allergens. Longitudinal associations between each exposure and health outcome pair were analysed using generalized estimation equations (GEEs). RESULTS: The results of our longitudinal analyses of 5674 subjects do not support the research hypothesis that travelling abroad to different regions in Europe or beyond Europe and frequency of travelling increase prevalence of doctor-diagnosed asthma and allergic rhinitis, nose and eye symptoms and allergic sensitization up to 15 years of age. Furthermore, there was no indication of age-varying effects. CONCLUSIONS: Early life travelling does not seem to increase risk of atopic outcomes. Nevertheless, as we could not account for the type of visited environment or length of stay, these first findings should be interpreted with caution.

Residential greenness is differentially associated with childhood allergic rhinitis and aeroallergen sensitization in seven birth cohorts.

BACKGROUND: The prevalence of allergic rhinitis is high, but the role of environmental factors remains unclear. We examined cohort-specific and combined associations of residential greenness with allergic rhinitis and aeroallergen sensitization based on individual data from Swedish (BAMSE), Australian (MACS), Dutch (PIAMA), Canadian (CAPPS and SAGE), and German (GINIplus and LISAplus) birth cohorts (n = 13 016). METHODS: Allergic rhinitis (doctor diagnosis/symptoms) and aeroallergen sensitization were assessed in children aged 6-8 years in six cohorts and 10-12 years in five cohorts. Residential greenness was defined as the mean Normalized Difference Vegetation Index (NDVI) in a 500-m buffer around the home address at the time of health assessment. Cohort-specific associations per 0.2 unit increase in NDVI were assessed using logistic regression models and combined in a random-effects meta-analysis. RESULTS: Greenness in a 500-m buffer was positively associated with allergic rhinitis at 6-8 years in BAMSE (odds ratio = 1.42, 95% confidence interval [1.13, 1.79]) and GINI/LISA South (1.69 [1.19, 2.41]) but inversely associated in GINI/LISA North (0.61 [0.36, 1.01]) and PIAMA (0.67 [0.47, 0.95]). Effect estimates in CAPPS and SAGE were also conflicting but not significant (0.63 [0.32, 1.24] and 1.31 [0.81, 2.12], respectively). All meta-analyses were nonsignificant. Results were similar for aeroallergen sensitization at 6-8 years and both outcomes at 10-12 years. Stratification by NO2 concentrations, population density, an urban vs rural marker, and moving did not reveal consistent trends within subgroups. CONCLUSION: Although residential greenness appears to be associated with childhood allergic rhinitis and aeroallergen sensitization, the effect direction varies by location.

Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story: Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study.

BACKGROUND: Data on the long-term impact of hydrolyzed formulas on allergies are scarce. OBJECTIVE: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence. METHODS: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models. RESULTS: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula. CONCLUSION: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.

Cord blood n-3 LC-PUFA is associated with adiponectin concentrations at 10 years of age.

An elevated ratio of n-6 to n-3 long-chain (LC-) polyunsaturated fatty acids (PUFA) may be a potential risk factor for obesity development. N-3 LC-PUFA are thought to alter adiponectin concentrations, and thus may have a beneficial effect on weight development. We analysed the association between n-3 LC-PUFA concentrations in cord blood and adiponectin concentrations at 10 years. Fatty acid composition was measured in cord blood and at 10 years of age by gas chromatography, and adiponectin concentrations were measured only at 10 years of age in 237 children from the Munich LISAplus birth cohort study. Linear regression models assessed associations between n-3 LC-PUFA, n-6 LC-PUFA and the n-6/n-3 ratio in cord blood with adiponectin concentrations at 10 years of age. LC-PUFA were presented as percentages and categorized into tertiles. Regression models were adjusted for LC-PUFA percentages at 10 years of age and other potential confounding factors. Cord blood n-3 LC-PUFA tertiles were significantly associated with adiponectin concentrations in an inverse J-shaped relationship [2nd tertile versus 1st tertile: Beta=1.84 (SE=0.65), and 3rd tertile versus 1st tertile: 1.02 (0.68), p-value<0.01 (ANOVA)]. Further, cord blood n-6/n-3 ratios were significantly associated with adiponectin concentrations [2nd tertile versus 1st tertile: 0.14 (0.67), and 3rd tertile versus 1st tertile: -1.37 (0.68), p-value=0.03 (ANOVA)]. The cord blood n-6 LC-PUFA tertiles were not associated with adiponectin concentrations. Our results suggest that a higher n-3 LC-PUFA concentrations and a lower n-6/n-3 ratio in cord blood are associated with higher adiponectin concentrations at 10 years of age.

Parental allergic disease before and after child birth poses similar risk for childhood allergies.

Whether the strength of associations between parental and child allergic diseases differs by whether the first onset of the parental disease is before or after a child's birth has never been examined and is the aim of this study. Yearly childhood asthma, allergic rhinitis, and eczema diagnoses were longitudinally regressed against the effect of a parental disease (pre- vs post-child birth) of the same type separately for each parent using generalized estimation equations. Both a maternal and paternal history of asthma were associated with childhood asthma prevalence up to 15 years of age. Effect estimates were similar for parental asthma with first onset before and after the birth of the child. The results for allergic rhinitis and eczema were less consistent. Parental allergic diseases with first onsets before and after the birth of a child both pose risks to childhood allergic disease in the offspring, especially for asthma.

Mother's body mass index and food intake in school-aged children: results of the GINIplus and the LISAplus studies.

BACKGROUND/OBJECTIVES: Mother's body mass index (BMI) is a strong predictor of child BMI. Whether mother's BMI correlates with child's food intake is unclear. We investigated associations between mother's BMI/overweight and child's food intake using data from two German birth cohorts. SUBJECTS/METHODS: Food intakes from 3230 participants were derived from parent-completed food frequency questionnaires. Intakes of 11 food groups were categorized into three levels using group- and sex-specific tertile cutoffs. Mother's BMI and overweight were calculated on the basis of questionnaire data. Multinomial regression models assessed associations between a child's food intake and mother's BMI/overweight. Linear regression models assessed associations between a child's total energy intake and mother's BMI. Models were adjusted for study region, maternal education, child's age, sex, pubertal status and energy intake and the BMIs of the child and father. RESULTS: Mothers' BMI was associated with high meat intake in children (adjusted relative risk ratio (RRR (95% confidence interval))=1.06 (1.03; 1.09)). Mothers' overweight was associated with the meat intake (medium versus low RRR=1.30 (1.07; 1.59); high versus low RRR=1.50 (1.19; 1.89)) and egg intake (medium versus low RRR=1.24 (1.02; 1.50); high versus low RRR=1.30 (1.07; 1.60)) of children. There were no consistent associations for rest of the food groups. For every one-unit increase in mothers' BMI, the total energy intake in children increased by 9.2 kcal (3.7; 14.7). However, this effect was not significant after adjusting for children's BMI. CONCLUSIONS: Our results suggest that mother's BMI and mother's overweight are important correlates of a child's intake of energy, meat and eggs.

Epidemiology of urticaria in infants and young children in Germany--results from the German LISAplus and GINIplus Birth Cohort Studies.

BACKGROUND: Although urticaria is considered one of the most frequent skin diseases, reliable epidemiologic data are scarce. OBJECTIVE: To evaluate the incidence and cumulative prevalence of urticaria in infants and children up to age of 10, to characterize the relationship of specific IgE levels (food and inhalative allergens) with urticaria, and to monitor the joint occurrence of urticaria with other diseases, such as eczema, asthma, and hay fever. METHODS: The study population consisted of two prospective birth cohort studies: the LISAplus and GINIplus studies. Information on physician-diagnosed urticaria, asthma, eczema, or hay fever was collected using self-administered questionnaires completed by the parents. Blood samples were drawn, and specific immunoglobulin E measured at 2 (only LISAplus), 6 and 10 yr of age. RESULTS: The incidence of urticaria was approximately 1% per year of age. The cumulative prevalence of urticaria in children up to the age of 10 yr was 14.5% for boys and 16.2% for girls. Cumulative prevalence of urticaria at the age of ten was significantly (p < 0.05) associated with allergic sensitization to peanut, soy, and wheat flour, but not with inhalant allergens. Both a parental history of atopy/urticaria and the children's diagnosis of asthma, eczema, and hay fever were strongly related (p < 0.0001) to the occurrence of urticaria. CONCLUSIONS: Urticaria is a frequent event during childhood, with highest incidence in infants and preschool children. Comorbidity with atopic disease is high.

Glutathione-S-transferase P1, early exposure to mould in relation to respiratory and allergic health outcomes in children from six birth cohorts. A meta-analysis.

BACKGROUND: There are conflicting study results regarding the association of exposure to visible mould and fungal components in house dust with respiratory and allergic diseases in children. It has been suggested that functional polymorphisms of the GSTP1 gene may influence the risk for allergic disorders through an impaired defence against oxidant injury. METHODS: We examined in six birth cohorts of over 14 000 children whether the association between early exposure to reported mould at home in relation to respiratory and allergic diseases is modified by a single nucleotide polymorphism of the GSTP1 gene. RESULTS: We observed a positive association of mould exposure with nasal symptoms (2-10 year) aOR: 1.19 (1.02-11.38). Further, there was a borderline significant increased risk of rhinoconjunctivitis (6-8 year) in children homozygous for the minor allele Val/Val, aOR: 1.25 (0.98-1.60). In stratified analyses, subjects homozygous for the minor allele and exposed to mould at home were at increased risk for early wheezing aOR: 1.34 (1.03-1.75), whereas the major allele may confer susceptibility for later nasal outcomes, (6-8 year) aOR: 1.20 (1.00-1.45) and (2-10 year) aOR: 1.30 (1.04-1.61), respectively. For none of the health outcomes studied, we found gene by environment interactions. CONCLUSION: A genetic influence of the GSTP1 gene cannot be ruled out, but the magnitude of the effect is a matter of further research. In conclusion, the interplay between gene and environments is complex and remains subject of further study.

[Two German Birth Cohorts: GINIplus and LISAplus]. / Die zwei deutschen Geburtskohorten GINIplus und LISAplus.

Numerous chronic diseases in childhood and adulthood have their origins in perinatal life and are potentially influenced by trans-generational epigenetic processes. Therefore, prospective birth cohorts can substantially contribute to our knowledge about the etiology of diseases including modifiable risk factors. The two population-based German birth cohorts GINIplus and LISAplus aim to describe the natural course of chronic diseases and intermediate phenotypes in childhood and its determinants, and to identify potential genetic effect modifications. In the mid-1990s, 5,991 (GINIplus) and 3,097 (LISAplus) healthy, term newborns were recruited for long-term follow-up in four regions of Germany. The follow-up rate for the first 10 years was about 55%. We analyzed the growth and development of overweight, infections and allergic diseases, mental and oral health, metabolic and inflammatory parameters and the role of potential risk factors including genetics. The results of these two birth cohorts substantially contribute to the current knowledge about the natural course of these health parameters. These data were included in many international projects and consortia for purposes of international comparisons of prevalence and consistency of findings, and to increase the power of the analyses.

FADS gene cluster modulates the effect of breastfeeding on asthma. Results from the GINIplus and LISAplus studies.

BACKGROUND: The protective effect of breastfeeding (BF) on the development of asthma has been widely recognized, even if not all results have been consistent. Gene variants of the FADS gene cluster have a major impact on fatty acid composition in blood and in breast milk. Therefore, we evaluated the influence of the FADS1 FADS2 gene cluster polymorphisms on the association between BF and asthma. METHODS: The analysis was based on data (N=2245) from two German prospective birth cohort studies. Information on asthma and BF during the first 6 months was collected using questionnaires completed by the parents. Logistic regression modelling was used to analyse the association between exclusive BF and ever having asthma stratified by genotype. RESULTS: In the stratified analyses, BF for 3 or 4 months after birth had a protective effect for heterozygous and homozygous carriers of the minor allele (adjusted odds ratio between 0.37 (95% CI: 0.18-0.80) and 0.42 (95% CI: 0.20-0.88). Interaction terms of BF with genotype were significant and ranged from -1.17 (P-value: 0.015) to -1.33 (0.0066). Moreover, heterozygous and homozygous carriers of the minor allele who were exclusively breastfed for 5 or 6 months after birth had a reduced risk of asthma [0.32 (0.18-0.57) to 0.47 (0.27-0.81)] in the stratified analyses. For individuals carrying the homozygous major allele, BF showed no significant effect on the development of asthma. CONCLUSIONS: The association between exclusive BF and asthma is modified by the genetic variants of FADS genotypes in children.

FADS gene variants modulate the effect of dietary fatty acid intake on allergic diseases in children.

BACKGROUND: The association between dietary fatty acid intake and the development of atopic diseases has been inconsistent. This could be due to inter-individual genetic differences in fatty acid metabolism. OBJECTIVE: The aim of the current study was to assess the influence of FADS1 FADS2 gene cluster polymorphisms on the association between dietary fatty acid intake and atopic diseases and allergic sensitization in 10-year-old children. METHODS: The analysis was based on data from two German prospective birth cohort studies. Data on margarine and fatty acid intake were collected using a food frequency questionnaire. Information on atopic diseases was collected using a questionnaire completed by the parents. Specific IgE against common food and inhalant allergens were measured. Six variants of the FADS1 FADS2 gene cluster (rs174545, rs174546, rs174556, rs174561, rs174575 and rs3834458) were tested. Logistic regression modelling, adjusted for gender, age, maternal education level and study centre, was used to analyse the association between fatty acid intake and atopic diseases stratified by genotype. RESULTS: No significant association was found between the six FADS single nucleotide polymorphisms (SNPs) and allergic diseases or atopic sensitization. The total n-3/total n-6 ratio was positive associated with an increased risk of hayfever in homozygous major allele carriers ranging from an adjusted odds ratios of 1.25 (95%-CI: 1.00-1.57) to 1.31 (95%-CI: 1.01-1.69) across the six tested SNPs although this association was not significant anymore after correcting for multiple testing. Daily margarine intake was significantly associated with asthma [1.17 (1.03-1.34) to 1.22 (1.06-1.40)] in individuals carrying the homozygous major allele. This association was also significant after correcting for multiple testing. CONCLUSIONS & CLINICAL RELEVANCE: The association between dietary intake of fatty acids and allergic diseases might be modulated by FADS gene variants in children.