Assisted conception and the risk of CHD: a case-control study.

Epidemiological studies suggest a higher prevalence of congenital malformations in children conceived through assisted reproductive technologies. There are a few studies that address CHD specifically and most have examined data from registries. We examined the relationship between CHD and assisted conception using data collected in a specialist paediatric cardiac service in the United Kingdom. Between April, 2010 and July, 2011, the parents of children attending paediatric cardiology clinics at the Royal Brompton Hospital, London, were invited to complete a questionnaire that enquired about the nature of their child's conception, the route for their original referral, and a number of potential confounding exposures. "Cases" were defined as children diagnosed with one or more carefully defined CHDs and "controls" as those with normal hearts. Of 894 new attendees with complete data, half of them were cases (n=410, 45.9%). The overall prevalence of assisted conception was 5.4% (n=44). Logistic regression analysis demonstrated a non-significant increase in the crude odds for the use of assisted reproduction (odds ratio 1.21, 95% confidence interval 0.66-2.22) in this group. After adjustment for gestation, parity, year of birth, and maternal age, the odds ratio reduced (odds ratio 0.95, 95% confidence interval 0.48-1.88). Increased rates of assisted conception were observed in a number of CHD subgroups, although no significant differences were found. These findings do not suggest an overall association between CHD and assisted reproduction in this population.

A polymorphism affecting MYB binding within the promoter of the PDCD4 gene is associated with severe asthma in children.

A previous genome-wide association study in asthma revealed putative associations that merit further investigation. In this study, the genome-wide significant associations of SNPs at the 5% false discovery rate were examined in independent groups of severe asthmatics. The panel consisted of 397 severe asthmatic adults, 116 severe asthmatic children, and a collection of 207 family-trios with an asthmatic proband. Three SNPs in the PDCD4 gene (rs6585018:G>A, rs1322997:C>A, and rs34104444:G>A) were significantly associated with severe childhood asthma (P values: 0.003, 0.002, 0.004) and total immunoglobulin E (IgE) levels (P values: 0.034, 0.041, 0.052). In an independent group of 234 asthmatic children and 652 controls, PDCD4 SNPs rs1407696:T>G and rs11195360:T>C were associated with total IgE levels (P values: 0.006, 0.014). In silico analysis of PDCD4 locus showed that rs6585018:G>A had the potential to affect MYB transcription factor binding, shown to act as a PDCD4-transcription inducer. Electromobility shift assays and reporter assays revealed that rs6585018:G>A alters MYB binding thereby influencing the expression of PDCD4. SNPs within MYB itself confer susceptibility to eosinophilia and asthma. Our association between a variant MYB binding site in PDCD4 and the severest form of childhood asthma therefore suggests that PDCD4 is a novel molecule of importance to asthmatic inflammatory responses.