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.

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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.

Objective. Childhood asthma is a frequent cause of absenteeism that affects school performance. We aimed to investigate the impact of asthma on absenteeism and school performance level of elementary and high school students. Methods. Data about sociodemographics, absenteeism, and academic achievement were obtained from 1539 students attending 98 schools in Greece. School performance was assessed for the last two years of school attendance using parents' and teachers' reports and grade point average promotion. Results. The mean of the days of absence of students with asthma was higher compared to the healthy students (6.2 ± 11.7 versus 0.3 ± 3.1, resp., P < 0.001). Students with reduced healthcare use presented less absenteeism than those with increased healthcare use for asthma (4.3 ± 8.6 versus 12.4 ± 17.0 days, resp., P < 0.001). Asthma and healthcare use for asthma accounted for an overall estimated variability in absence days of 13.8% and 9%, respectively. Absenteeism was associated with poor school performance for the last two years of school (P = 0.002) and with lower grade point promotion in elementary school students (P = 0.001) but not in high school students (P = 0.316). Higher level of parental education was associated with better school performance (P < 0.001). Asthma was associated with a decreased possibility for excellent performance (OR = 0.64, P = 0.049, 95%CI = 0.41–1.00) in elementary students. Students with asthma using inhalers were four times more likely to perform excellently in elementary school (OR = 4.3, P = 0.028, 95%CI = 1.17–15.95) than their asthmatic peers with alternative asthma treatments. Conclusions. Asthma and increased healthcare use enhance school absenteeism. Inhaled steroid use and the higher parental education level were the most important predicting factors for good school performance in elementary school asthmatic children.

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.