BACKGROUND Suggestive, but not conclusive, studies implicate many genetic variants in oral cleft etiology. We used a large, ethnically homogenous study population to test whether reported associations between nonsyndromic oral clefts and 12 genes (CLPTM1, CRISPLD2, FGFR2, GABRB3, GLI2, IRF6, PTCH1, RARA, RYK, SATB2, SUMO1, TGFA) could be confirmed. METHODS Thirty-one single nucleotide polymorphisms (SNPs) in exons, splice sites, and conserved non-coding regions were studied in 509 patients with cleft lip with or without cleft palate (CLP), 383 with cleft palate only (CP), 838 mothers and 719 fathers of patients with oral clefts, and 902 controls from Ireland. Case-control and family-based statistical tests were performed using isolated oral clefts for the main analyses. RESULTS In case-control comparisons, the minor allele of PTCH1 A562A (rs2066836) was associated with reduced odds of CLP (OR: 0.29, 95% CI: 0.13–0.64 for homozygotes) whereas the minor allele of PTCH1 L1315P (rs357564) was associated with increased odds of CLP (OR: 1.36, 95% CI: 1.07–1.74 for heterozygotes and OR: 1.56, 95% CI: 1.09–2.24 for homozygotes). The minor allele of one SUMO1 SNP, rs3769817 located in intron 2, was associated with increased odds of CP (OR: 1.45, 95% CI: 1.06–1.99 for heterozygotes). Transmission disequilibrium was observed for the minor allele of TGFA V159V (rs2166975) which was over-transmitted to CP cases (P=0.041). CONCLUSIONS For 10 of the 12 genes, this is the largest candidate gene study of nonsyndromic oral clefts to date. The findings provide further evidence that PTCH1, SUMO1, and TGFA contribute to nonsyndromic oral clefts.

BACKGROUND-Cleft lip with or without cleft palate (CLP) and cleft palate only (CPO) have an inherited component and, many studies suggest, a relationship with folate. Attempts to find folaterelated genes associated with clefts have, however, often been inconclusive. This study examined four SNPs related to folate metabolism (MTHFR 677 C→T, MTHFR 1298 A→C, MTHFD1 1958 G→A, and TC II 776 C→G) in a large Irish population to clarify their relationship with clefts.

The National Drug-Related Deaths Index (NDRDI) reports on poisoning deaths (also known as overdose), which are deaths in the general population due to the toxic effect of a drug or combination of drugs, and on non-poisonings, which are deaths as a result of trauma, such as hanging, or medical reasons, such as cardiac events, among people who use drugs. The latest figures from the NDRDI show that 376 people died in 2017 from poisoning deaths and that 410 non-poisoning deaths occurred among people who used drugs. 1,2 The newsletter of Ireland's focal point to the EMCDDA Drug-related deaths and deaths among people who use drugs in Ireland, 2008-2017 In this issue National Drugs Forum 2019 See page 06 09 Drug treatment figures 22 Ethnic identifiers 18 EU drug markets 12 My World survey 12 Growing Up in Ireland survey Drugnet Ireland is produced in collaboration with the HRB National Drugs Library. To have Drugnet Ireland delivered to your desktop, sign up at www.drugsandalcohol.ie Minister of State with responsibility for Health Promotion and the National Drugs Strategy, Catherine Byrne TD, speaking at the 2019 National Drugs Forum in Croke Park Contents COVER STORY Drug-related deaths and deaths among people who use drugs in Ireland, 2008-2017 01 POLICY AND LEGISLATION British-Irish Council in Dublin 05 National Drugs Forum 2019 06 PREVALENCE AND CURRENT SITUATION Drug treatment in Ireland 2012-2018 09 NDTRS drug and alcohol treatment data for 2004-2018 available online 12 Alcohol and drug use among young people and adolescents in Ireland-results from My World and Growing Up in Ireland surveys 12 Alcohol treatment figures from the NDTRS, 2012-2018 15 Repeated cross-sectional study of factors associated with pregabalinpositive poisoning deaths in Ireland 16 EU drug markets report

The high percentage of individuals with a diagnosis of alcohol dependency that died as a result of epilepsy and who have no antiepileptic drugs in their system at the time of their death, highlights the need for preventative measures for this at-risk group.