A short period of breastfeeding in infancy, excessive house cleaning, absence of older sibling, and passive smoking are related to more severe atopic dermatitis in children.

BACKGROUND: Atopic dermatitis (AD) is one of the most common, chronic or chronically relapsing inflammatory skin diseases that affect children. Multiple genetic and environmental factors appear to regulate the pathogenesis of AD. OBJECTIVES: Our aim was to investigate the possible association between family, social, dieting, atopic and environmental factors and the severity of AD evaluated by SCORAD scores in children. MATERIALS & METHODS: The study group included 100 children with AD who attended a paediatric dermatology outpatient clinic with a median age of 18.5 months. The diagnosis of AD was established on the basis of the clinical criteria according to the American Dermatology Society, while the SCORAD score was used to evaluate disease severity. RESULTS: Multivariate linear regression analysis disclosed that excessive cleanliness (p<0.001), RAST level greater than 0.7 KU/l (p<0.001), breastfeeding for less than two months (p = 0.001), and the absence of an older sibling (p = 0.049) were statistically significant independent determinants for high SCORAD scores. Multivariate logistic regression analysis showed that excessive cleanliness (p<0.001) was the strongest independent risk factor for severe AD (SCORAD>36) (aOR: 59.4; 95% CI: 10.9-322.6). RAST level greater than 0.7 KU/l (aOR: 7.9; 95% CI: 1.5-41.0; p = 0.014) and severe passive smoking (aOR: 4.6; 95% CI: 1.0-22.1; p = 0.050) also showed a significant independent, but clearly weaker, association with severe AD. CONCLUSIONS: A short duration of breastfeeding, absence of older siblings, parental passive smoking, food allergens along with aeroallergens, and excessive cleanliness should be considered as negative prognostic factors, leading to a higher SCORAD score in children with AD.

Association of Asthma and Allergic Rhinitis With Sleep-Disordered Breathing in Childhood.

Objective: Asthma and allergic rhinitis (AR) are the most common chronic conditions in childhood and have previously been linked to sleep-related breathing disorder (SRBD). Aim of the study was to examine the association between SRBD risk and asthma control in children with asthma and with or without AR. Methods: The assessment of FeNO and pulmonary function tests were performed in 140 children (65 with asthma, 57 with both asthma, and AR, 18 with only AR). Children with asthma completed the childhood Asthma Control Test (c-ACT), and the Sleep-Related Breathing Disorder scale, extracted from the Pediatric Sleep Questionnaire (PSQ). C-ACT scores ≤ 19 are indicative of poor asthma control whereas SRBD from PSQ scores ≥ 0.33 are suggestive of high risk for SRBD. Results: Mean age ± SD was 7.8 ± 3.1 years. Mean PSQ ± SD and c-ACT ± SD scores were 0.17 ± 0.14 and 24.9 ± 3.2, respectively. High risk for SRBD was identified in 26 children. Children at high risk for SRBD had significantly decreased c-ACT score (P = 0.048), verified by a negative association between c-ACT and PSQ-SRBD scores (r = -0.356, P < 0.001). Additionally a difference in diagnosis distribution between children at high or low risk for SRBD was observed. More specifically, among children at high risk, 88.5% were diagnosed with both atopic conditions, while this percentage among children at low risk was 29.8%. Asthma was mainly diagnosed in the latter group (P < 0.001). Conclusions: Poor asthma control is associated with SRBD. The presence of AR in children with asthma seems to increase the prevalence of SRBD in that particular population, requiring further investigation toward this direction.

Genetic polymorphisms of drug-metabolizing enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 in the Greek population.

The aim of the present study was to determine the prevalence of the most common allelic variants of the polymorphic cytochrome P450 (CYP) enzymes CYP2D6, CYP2C9, CYP2C19 and CYP3A5 and to predict the genotype frequency for each polymorphism in the Greek population. DNA isolated from peripheral blood samples derived from 283 non-related Greek ethnic subjects was used to determine the frequency of CYP2D6*3, CYP2D6*4, CYP2C9*2, CYP2C9*3 and CYP3A5*3 allelic variants by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method, CYP2C19*2 and CYP2C19*3 with allelic specific amplification (PCR-ASA), and CYP2D6*2 (gene duplications) by long PCR analysis. The allelic frequencies (out of a total of 566 alleles) for CYP2D6*3 and CYP2D6*4, were 2.3% and 17.8%, respectively, while gene duplications (CYP2D6*2) were found in 7.4% of the subjects tested. For CYP2C9*2 and CYP2C9*3 polymorphisms the allelic frequencies were 12.9% and 8.13% respectively. For CYP2C19, the *2 polymorphism was present at an allelic frequency of 13.1%, while no subjects were found carrying the CYP2C19*3 allele. Finally, the CYP3A5*3 allele was abundantly present in the Greek population with an allelic frequency of 94.4%. Overall our results show that the frequencies of the common defective allelic variants of CYP2C9, CYP2C19 and CYP3A5 in Greek subjects are similar to those reported for several other Caucasian populations. Finally, a high prevalence of CYP2D6 gene duplication among Greeks was found, a finding that strengthens the idea that a South/North gradient exists in the occurrence of CYP2D6 ultrarapid metabolizers in European populations.

Asthma phenotypes in children and stratified pharmacological treatment regimens.

INTRODUCTION: Asthma is the most common inflammatory disease in childhood. The interaction of genetic, environmental and host factors may contribute to the development of childhood asthma and defines its progress, including persistence and severity. Until now, various classifications of childhood asthma phenotypes have been suggested based on patient's age during onset of symptoms, type of inflammatory cells, response to treatment and disease severity. Many efforts have been carried out to identify childhood asthma phenotypes and to clarify which are the risk factors that define asthma prediction and the response to therapy. The identification of asthma phenotypes has not only prognostic but also therapeutic role. However, the classification of asthma phenotypes is complex due to the heterogeneity of the disease. Areas covered: The current childhood asthma phenotypes and the new therapeutic strategies for each phenotype are reviewed. Expert commentary: There are multiple phenotypes in childhood asthma and it is crucial to define them before the initiation of personalized treatment. Both the therapeutic strategy and monitoring should follow the recent guidelines.

Endothelial nitric oxide synthase gene polymorphisms are associated with sensitization to seasonal aeroallergens in asthmatic children.

BACKGROUND: Childhood asthma phenotype is the consequence of interaction between environment and genetic factors. Nitric oxide (NO) formation is affected by polymorphisms in nitric oxide synthase (NOS) enzymes, which play a significant role as inflammatory factors in the airways. This study was undertaken to estimate the correlation of -786C>T and 894G>T polymorphisms of the eNOS gene with the sensitization of asthmatic children to common aeroallergens. METHODS: A total of 193 asthmatic children and 96 healthy controls, who were of Mediterranean origin, living in the same geographical area, were enrolled in the study. 894G>T and -786T/C polymorphisms of the eNOS gene were analyzed using a PCR-RFLP method. RESULTS: The 894GG genotype was more frequent (68.6%) in children with asthma sensitized to Oleaeuropaea than in those with asthma non-sensitized (43.0%) (P=0.004). Likewise, -786TT genotype frequency was higher in children with asthma sensitized to Oleaeuropaea (51.0%) than in those with asthma nonsensitized (31.7%) to this allergen (P=0.035). For the aeroallergens Parietariajudaica and mixed grass, the frequency of -786C allele carriage was associated with protection from sensitization to Parietariajudaica and mixed grass in asthmatic children (P=0.021 and P=0.017, respectively). In the healthy control group, the genotype frequencies for these polymorphisms were similar to genotype frequencies of children with asthma non-sensitized to these three specific aeroallergens. CONCLUSION: In children with asthma, 894G>T and -786T/C polymorphisms of the eNOS gene were correlated with sensitization to common seasonal aeroallergens.

Vitamin D receptor ApaI a allele is associated with better childhood asthma control and improvement in ability for daily activities.

Vitamin D levels have been suggested as a marker of disease severity in asthmatic children. Our aim was to investigate possible associations between the vitamin D receptor (VDR) FokI, BsmI, ApaI, and TaqI polymorphisms and asthma susceptibility and control in children. 127 Greek children with asthma and 91 healthy controls were genotyped for VDR FokI, BsmI ApaI, and TaqI polymorphisms using Sequenom MassARRAY iPLEX platform. Asthma control was assessed according to the Global Initiative for Asthma guidelines (GINA) and Childhood Asthma Control Test (C-ACT) and, for the first time, tested for its possible association with VDR SNPs. Asthmatic children were grouped as "controlled (n=49)", "partially controlled (n=38)," and "uncontrolled (n=40)," according to GINA classification. No association was found between VDR polymorphisms and asthma prevalence. Asthmatic children with the VDR ApaI aa genotype had significantly higher C-ACT score compared with asthmatic children carrying the AA/AC VDR ApaI genotypes (p=0.011). The frequency of VDR ApaI aa genotype was significantly higher in controlled asthma group (n=92) than uncontrolled asthma group (n=35), according to C-ACT (24.5% vs 0.0%, p<0.001) and GINA (32.7% vs 7.5%, p=0.001). Also, VDR ApaI aa genotype was negatively associated with limitation in daily activities because of asthma (p=0.004). VDR ApaI aa genotype was positively associated with well-controlled asthma according to GINA and C-ACT questionnaire and negatively associated with decreased limitation in daily activities in asthmatic children, further supporting the importance of Vitamin D pathway in asthma.

G894T polymorphism of eNOS gene is a predictor of response to combination of inhaled corticosteroids with long-lasting ß2-agonists in asthmatic children.

AIM: Nitric oxide synthase enzymes have an important role in airway inflammation in asthmatic children. In the present study, the association between eNOS gene polymorphisms and response to inhaled corticosteroids (ICS) and long-lasting ß(2)-agonists (LABAs) was investigated. PATIENTS & METHODS: A total of 81 asthmatic children treated with ICS plus LABAs and 96 healthy controls were genotyped for eNOS G894T and -786T/C polymorphisms and their haplotypes using the PCR-RFLP method. RESULTS: G894T and -786T/C polymorphisms were not associated with asthma susceptibility. Among asthmatic children, 894TT carriers had higher change in forced expiratory volume in 1 s (FEV(1)) in response to ICS plus LABAs compared with 894GG carriers (21.9 ± 3.8 vs 1.6 ± 1.9%; p < 0.001). In responders (FEV(1) change ≥7.5%), frequency of 894TT genotype was significantly higher than in nonresponders (26.2 vs 2.6%, p < 0.001). Results for the -786T/C polymorphism alone were less clear and in most cases nonsignificant. CONCLUSION: The G894T polymorphism was associated with response to ICS and may serve as a useful pharmacogenetic marker of response to ICS plus LABAs in asthmatic children.

The serotonin transporter promoter polymorphism (5-HTTLPR) is associated with type 2 diabetes.

BACKGROUND: The serotonergic system contributes substantially to the regulation of glucose homeostasis and feeding. 5-HTTLPR is a serotonin transporter (5-HTT) gene-linked polymorphic region that regulates the transcriptional activity of 5-HTT. Our aim was to investigate the possible association of 5-HTTLPR polymorphism with type 2 diabetes mellitus and obesity. METHODS: Study population consisted of 252 subjects diagnosed with Type 2 DM and 211 non-diabetic subjects, all Caucasians of Greek ethnic origin. Genomic DNA was extracted from peripheral blood and analyzed for 5-HTTLPR polymorphism with a novel PCR protocol. RESULTS: The frequency of SS and SL genotypes of HTTLPR was significantly higher in the diabetic group (77.0%) than in the non-diabetic group (61.6%) (P<0.001). The genetic risk of Type 2 DM for subjects carrying at least one S allele was increased compared to non-diabetic subjects (OR=2.08, 95% CI=1.39-3.12). When subjects were divided according to BMI status, the frequency of S allele carriers was similar in obese and non-obese subjects. CONCLUSIONS: The S allele of 5-HTTLPR is strongly associated with the presence of Type 2 DM. This association appears to be direct and not dependent on obesity status. Therefore, 5-HTTLPR LL genotype might be protective for development of Type 2 DM.

Association of polymorphisms of the serotonergic system with smoking initiation in Caucasians.

BACKGROUND: The serotonergic system may be implicated in susceptibility to nicotine dependence as nicotine increases 5-hydroxytryptamine (5-HT) release in brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. We examined the association of polymorphisms of genes involved in release and receptor function of 5-HT with cigarette smoking initiation in subjects of Caucasian origin. METHODS: 5-HTTLPR polymorphism of the 5-HT transporter gene and -759C/T (rs3813929) and -697G/C (rs518147) polymorphisms of the 5-HT(2C) receptor gene were analyzed in 172 smoking initiators and 254 non-initiators, using PCR-RFLP method. Smoking behavior was assessed with a questionnaire about tobacco use. RESULTS: We found no differences in the frequency of the 5-HTTLPR genotypes between smoking initiators and non-initiators. However, the frequency of 5-HT(2C) -759T allele was significantly higher in non-initiators than smoking initiators (29.5% vs 16.3%, p=0.002) and the same was true for 5-HT(2C) -697C allele carriers (48.8% vs 34.9%, p=0.004). Sex-dependent analysis revealed that these increased frequencies of -759T and -697C allele carriers were present only in males. No association was observed between any quantitative measures of smoking and these three polymorphisms. CONCLUSIONS: 5-HTTLPR polymorphism was not associated with smoking initiation in either male or female subjects. However, significant association was found between 5-HT(2C) receptor gene polymorphisms and smoking initiation in male Caucasian subjects.

The -759C/T polymorphism of the 5-HT2C receptor is associated with type 2 diabetes in male and female Caucasians.

OBJECTIVES: Type 2 diabetes mellitus and obesity constitute serious health problems. Studies reveal that the 5-HT2C receptor contributes substantially to the regulation of a wide variety of behavioral and physiological processes including feeding and glucose homeostasis. Our aim was to determine the possible association of the -759C/T polymorphism of the 5-HT2C receptor gene with type 2 diabetes and obesity in male and female individuals Caucasian origin. METHODS: The study population consisted of 151 patients diagnosed with type 2 diabetes and 164 nondiabetic patients, all of Greek origin. Genomic DNA was extracted from peripheral blood and analyzed for the -759C/T polymorphism of the 5-HT2C receptor gene using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The frequency of T allele of the -759C/T polymorphism of the 5-HT2C receptor was significantly lower in the diabetic group (12.6%) than in the nondiabetic group (23.3%) (P=0.003). The genetic risk of type 2 diabetes for patients not carrying the T allele was increased compared with nondiabetic patients (odds ratio (OR)=2.34, 95% confidence interval (CI)=1.36-4.02). The reduced frequency of T allele was present both in male [10% in patients with diabetes and 21.6% in patients without diabetes (P=0.041)] and female patients [14.1% in patients with diabetes and 24.3% in patients without diabetes (P=0.030)]. In contrast, the frequency of T allele was similar in obese (16.4%) and nonobese (17.1%) patients. CONCLUSIONS: Lower frequency of -759T allele of the 5- HT2C receptor gene was associated with type 2 diabetes but not with obesity in male and female Caucasians. Thus, this polymorphism might constitute a prognostic marker for diabetic risk.