Current studies of gene × air pollution interaction typically seek to identify unknown heritability of common complex illnesses arising from variability in the host's susceptibility to environmental pollutants of interest. Accordingly, a single component generalized linear models are often used to model the risk posed by an environmental exposure variable of interest in relation to a priori determined DNA variants. However, reducing the phenotypic heterogeneity may further optimize such approach, primarily represented by the modeled DNA variants. Here, we reduce phenotypic heterogeneity of asthma severity, and also identify single nucleotide polymorphisms (SNP) associated with phenotype subgroups. Specifically, we first apply an unsupervised learning algorithm method and a non-parametric regression to find a biclustering structure of children according to their allergy and asthma severity. We then identify a set of SNPs most closely correlated with each sub-group. We subsequently fit a logistic regression model for each group against the healthy controls using benzo[a]pyrene (B[a]P) as a representative airborne carcinogen. Application of such approach in a case-control data set shows that SNP clustering may help to partly explain heterogeneity in children's asthma susceptibility in relation to ambient B[a]P concentration with greater efficiency.

• Klíčová slova
• air pollution, asthma, gene-environment interaction, polycyclic aromatic hydrocarbon, single nucleotide polymorphism,
• MeSH
• algoritmy MeSH
• benzopyren toxicita   MeSH
• bronchiální astma chemicky indukované   genetika   MeSH
• dítě MeSH
• genetická predispozice k nemoci * MeSH
• interakce genů a prostředí MeSH
• jednonukleotidový polymorfismus MeSH
• látky znečišťující vzduch toxicita   MeSH
• lidé MeSH
• multifaktoriální dědičnost * MeSH
• statistika jako téma MeSH
• strojové učení bez učitele MeSH
• studie případů a kontrol MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• znečištění ovzduší škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzopyren MeSH
• látky znečišťující vzduch MeSH

Functional deficiency of mannan-binding lectin (MBL) has been associated with adverse pregnancy outcome. Adverse events during pregnancy have also been described in women with autoimmune thyroid diseases (AITD), and thyroid hormones have been shown to influence serum levels of MBL. Therefore, the aim of this study was to analyse the impact of MBL-deficiency on the outcome of pregnancy in relation to the presence of AITD. Almost one year after delivery, we assessed serum MBL levels and MBL2-genotypes in 212 women positively screened for AITD in pregnancy. In 103 of these women, we could also measure MBL levels in frozen serum samples from the 9-12(th) gestational week, obtaining 96 pairs of MBL values (pregnancy vs. follow-up). As controls, 80 sera of pregnant women screened negatively for AITD were used. MBL2-genotyping was performed using multiplex PCR. Women with thyroid dysfunction and/or thyroid peroxidase antibodies (TPOAb) had lower MBL levels during pregnancy than controls, (3275 vs. 5000 ng/ml, p<0.05). The lowest levels were found in women with elevated thyroid-stimulating hormone (TSH) levels in the absence of TPOAb (2207 ng/ml; p<0.01 as compared to controls). MBL2 genotype distribution did not differ between subgroups. At a median follow-up period of 17 months (range: 3-78 months) after delivery, median MBL level had decreased further to 1923 ng/ml (p<0.0001) without significant changes in TSH. In an explorative survey, functional MBL-deficiency was neither linked to a history of spontaneous abortion, nor other obstetric complications, severe infections throughout life/pregnancy or antibiotics use in pregnancy. In conclusion, hypothyroidism during pregnancy is associated with decreased MBL levels, and the levels decreased further after delivery.

• MeSH
• autoantigeny krev   MeSH
• autoimunitní tyreoiditida krev   MeSH
• autoprotilátky krev   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• jodidperoxidasa krev   MeSH
• komplikace těhotenství krev   MeSH
• lektin vázající mannosu krev   MeSH
• lidé MeSH
• následné studie MeSH
• proteiny vázající železo krev   MeSH
• první trimestr těhotenství krev   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• thyreotropin krev   MeSH
• výsledek těhotenství * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• autoprotilátky MeSH
• biologické markery MeSH
• jodidperoxidasa MeSH
• lektin vázající mannosu MeSH
• MBL2 protein, human MeSH Prohlížeč
• proteiny vázající železo MeSH
• thyreotropin MeSH
• TPO protein, human MeSH Prohlížeč