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Unaffected Controls (unaffected + control)
Selected AbstractsConfirmation of the role of ATG16l1 as a Crohn's disease susceptibility geneINFLAMMATORY BOWEL DISEASES, Issue 8 2007J.R. Fraser Cummings MRCP(UK) Abstract Background: A German genome-wide nonsynonymous single nucleotide polymorphism (nsSNP) association study identified ATG16L1 as a Crohn's disease (CD) susceptibility gene. The association appeared to be confined to the nsSNP rs2241880 and was confirmed in 2 German independent case-control collections (combined P = 4.0 × 10,8, odds ratio [OR] 1.45; 95% confidence interval [CI]: 1.21-1.74), a CD transmission disequilibrium test (TDT) collection, and an independent UK cohort. A weak statistical interaction with CARD15 was demonstrated. No association with ulcerative colitis (UC) was demonstrated. The aims of the study were to replicate the association with CD, examine subphenotype associations and statistical interactions with CARD15, IL23R, and the IBD5 risk haplotype, as well as explore the association with UC. Methods: The study included 645 CD and 676 UC rigorously phenotyped patients recruited from a single UK center. Unaffected controls comprised either spouses of patients (141) or individuals recruited from well-person clinics (1049). The nsSNP rs2241880 was genotyped using MassArray (Sequenom). Results: A strong association with CD was demonstrated (P = 2.33 × 10,7, OR 1.45 [1.25,1.67]), but no significant association was demonstrated with any subphenotype. We failed to replicate the reported interaction between rs2241880 and the CARD15 low-risk haplotypes dd and Dd. No significant statistical interaction with the 3 known CD susceptibility genes was seen. No association with UC susceptibility (P = 0.37, OR 1.06 [0.93-1.22]), or any UC subphenotype was identified. Conclusions: We confirmed the findings that ATG16L1 is a CD susceptibility gene and found no evidence of interaction with CARD15, IL23R, or IBD5. (Inflamm Bowel Dis 2007) [source] Community-based, Prospective, Controlled Study of Obstetric and Neonatal Outcome of 179 Pregnancies in Women with EpilepsyEPILEPSIA, Issue 1 2006Katriina Viinikainen Summary:,Purpose: This study evaluated obstetric and neonatal outcome in a community-based cohort of women with active epilepsy (WWAE) compared with the general pregnant population receiving modern obstetric care. Methods: We reviewed the total population who gave birth between January 1989 and October 2000 at Kuopio University Hospital. Obstetric, demographic, and epilepsy data were collected prospectively from 179 singleton pregnancies of women with epilepsy and from 24,778 singleton pregnancies of unaffected controls. The obstetric data from the pregnancy register was supplemented with detailed neurologic data retrieved from the medical records. The data retrieved were comprehensive because of a follow-up strategy according to a predecided protocol. Results: During pregnancy, the seizure frequency was unchanged, or the change was for the better in the majority (83%) of the patients. We found no significant differences between WWAE and controls in the incidence of preeclampsia, preterm labor, or in the rates of caesarean sections, perinatal mortality, or low birth weight. However, the rate of small-for-gestational-age infants was significantly higher, and the head circumference was significantly smaller in WWAE. Apgar score at 1 min was lower in children of WWAE, and the need for care in the neonatal ward and neonatal intensive care were increased as compared with controls. The frequency of major malformations was 4.8% (,0.6,10.2%; 95% confidence interval) in the 127 children of WWAE. Conclusions: Pregnancy course is uncomplicated and neonatal outcome is good in the majority of cases when a predecided protocol is used for the follow-up of WWAE in antenatal and neurologic care. Long-term follow-up of the neurologic and cognitive development of the children of WWAE is still needed. [source] Maternal plasma soluble fms-like tyrosine kinase-1 and free vascular endothelial growth factor at 11 to 13 weeks of gestation in preeclampsiaPRENATAL DIAGNOSIS, Issue 3 2010Ranjit Akolekar Abstract Objective To investigate the maternal plasma concentration of soluble fms-like tyrosine kinase-1 (sFlt-1) and free vascular endothelial growth factor (free-VEGF) at 11 to 13 weeks of gestation in patients destined to develop preeclampsia (PE) and to examine whether any possible differences in maternal plasma levels are related to uterine artery pulsatility index (PI) and maternal serum placental growth factor (PlGF). Methods Plasma free-VEGF, plasma sFlt-1, serum PlGF and uterine artery PI were measured at 11 to 13 weeks in 90 cases that subsequently developed PE and in 180 unaffected controls. Results In the majority of cases of PE and controls the levels of free-VEGF were undetectable. In the pregnancies that developed PE, compared to unaffected controls, uterine artery PI was higher, serum PlGF was lower but there was no significant difference in levels of sFlt-1. Conclusion Measurement of free-VEGF and sFlt-1 in maternal blood at 11 to 13 weeks of gestation is not useful in the prediction of pregnancies destined to develop PE. Copyright © 2010 John Wiley & Sons, Ltd. [source] Maternal serum placental protein 13 at 11,13 weeks of gestation in preeclampsiaPRENATAL DIAGNOSIS, Issue 12 2009Ranjit Akolekar Abstract Objective To examine the potential value of maternal serum concentration of placental protein 13 (PP13) at 11,13 weeks' gestation in screening for preeclampsia (PE). Methods Serum PP13, PAPP-A and uterine artery pulsatility index (PI) were determined in a case,control study of 208 cases that developed PE including 48 that required delivery before 34 weeks (early-PE) and 416 unaffected controls. Results Serum PP13 levels, expressed as multiples of the median (MoM) in the unaffected group, were significantly reduced in early-PE (0.83 MoM) but not in late-PE (0.96 MoM). In both early- and late-PE serum PAPP-A (0.55 and 0.84 MoM) was reduced and uterine artery PI (1.61 and 1.25 MoM) was increased. In PE pregnancies there was a significant association between serum PP13 and both uterine artery PI and serum PAPP-A (p < 0.0001 for both). Logistic regression analysis demonstrated that serum PP13 did not improve significantly the prediction of early-PE provided by a combination of maternal factors, uterine artery PI and PAPP-A. Conclusion PP13 is implicated in the pathogenesis of impaired placentation and subsequent development of early-PE but measurement of this placental product is unlikely to be useful in screening for the disease at 11,13 weeks. Copyright © 2009 John Wiley & Sons, Ltd. [source] Maternal serum ADAM12 levels in Down and Edwards' syndrome pregnancies at 9,12 weeks' gestationPRENATAL DIAGNOSIS, Issue 8 2006Jennie Laigaard Abstract Background Maternal serum ADAM12 is reduced, on average, in early first-trimester Down and Edwards' syndrome pregnancies but the extent of reduction declines with gestation. Here we study levels at 9,12 weeks when the marker might be used concurrently with other established markers. Methods Samples from 16 Down and 2 Edwards' syndrome cases were retrieved from storage and tested together with 313 unaffected singleton pregnancies using a semi-automated time-resolved immuno-fluorometric assay. Results were expressed in multiples of the gestation-specific median (MoM) based on regression. Results The median in Down syndrome was 0.94 MoM with a 10th,90th centile range of 0.22,1.63 MoM compared with 1.00 and 0.33,2.24 MoM in unaffected controls (P = 0.21, one-side Wilcoxon Rank Sum Test). The two Edwards' syndrome cases had values 0.31 and 2.17 MoM. Conclusions ADAM12 cannot be used concurrently with other markers in the late first trimester. However, it does have the potential to be used earlier in pregnancy either concurrently with other early markers or in a sequential or contingent protocol. More data will be required to reliably predict the performance of either approach. Copyright © 2006 John Wiley & Sons, Ltd. [source] Executive functions as endophenotypes in ADHD: evidence from the Cambridge Neuropsychological Test Battery (CANTAB)THE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 7 2010Susan Shur-Fen Gau Background:, Little is known about executive functions among unaffected siblings of children with attention deficit/hyperactivity disorder (ADHD), and there is lack of such information from non-Western countries. We examined verbal and nonverbal executive functions in adolescents with ADHD, unaffected siblings and controls to test whether executive functions could be potential endophenotypes for ADHD. Methods:, We assessed 279 adolescents (age range: 11,17 years) with a childhood diagnosis of DSM-IV ADHD, 136 biological siblings (108 unaffected, 79.4%), and 173 unaffected controls by using psychiatric interviews, the Wechsler Intelligence Scale for Children , 3rd edition (WISC-III), including digit spans, and the tasks involving executive functions of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Intra-dimensional/Extra-dimensional Shifts (IED), Spatial Span (SSP), Spatial Working Memory (SWM), and Stockings of Cambridge (SOC). Results:, Compared with the controls, adolescents with ADHD and unaffected siblings had a significantly shorter backward digit span, more extra-dimensional shift errors in the IED, shorter spatial span length in the SSP, more total errors and poorer strategy use in the SWM, and fewer problems solved in the minimum number of moves and shorter initial thinking time in the SOC. The magnitudes of the differences in the SWM and SOC increased with increased task difficulties. In general, neither persistent ADHD nor comorbidity was associated with increased deficits in executive functions among adolescents with ADHD. Conclusions:, The lack of much difference in executive dysfunctions between unaffected siblings and ADHD adolescents suggests that executive dysfunctions may be useful cognitive endophenotypes for ADHD genetic studies. [source] Chromosome 8q24 risk variants in hereditary and non-hereditary prostate cancer patients,THE PROSTATE, Issue 5 2008Jielin Sun Abstract Background Multiple variants in three regions at 8q24 are consistently found to be associated with prostate cancer (PCa) risk in population-based association studies. The role that these variants may play in familial prostate cancer risk has not been extensively investigated. Methods We evaluated 12 SNPs at three 8q24 regions using population-based association and family-based linkage and association methods in hereditary PCa (HPC) probands and their families, non-HPC patients, and unaffected screened controls, all recruited at Johns Hopkins Hospital. Results For multiple variants in Region 1 (e.g., rs1447295) and Region 2 (e.g., rs16901979), we found statistically significantly higher frequencies of previously identified risk alleles and genotypes in HPC probands than in unaffected controls. Furthermore, in Region 2 the risk alleles were statistically significantly more frequent in HPC probands than in non-HPC patients. Family-based transmission tests found risk alleles of SNPs in Region 2, but not in Regions 1 and 3, were significantly over-transmitted to affected men in these families. We found little evidence supporting PCa linkage at 8q24 in 168 HPC families, in part explained by the observation of multiple, different risk allele-containing haplotypes segregating in the vast majority of these families. Conclusions Our study further supports the presence of PCa susceptibility loci at 8q24, particular at Region 2, and also provides evidence that these SNPs play an important role in familial prostate cancer. Large family-based studies are needed to confirm our novel findings. Prostate 68: 489,497, 2008. © 2008 Wiley-Liss, Inc. [source] Assessing oxidative pathway genes as risk factors for bipolar disorderBIPOLAR DISORDERS, Issue 5 2010Janice M Fullerton Fullerton JM, Tiwari Y, Agahi G, Heath A, Berk M, Mitchell PB, Schofield PR. Assessing oxidative pathway genes as risk factors for bipolar disorder. Bipolar Disord 2010: 12: 550,556. © 2010 The Authors. Journal compilation © 2010 John Wiley & Sons A/S. Objectives:, There is a growing body of evidence implicating oxidative stress and the glutathione system in the pathogenesis of major psychiatric illnesses, including schizophrenia and bipolar disorder. Here we investigate whether genes involved in oxidative stress regulation are associated with increased risk for bipolar disorder. Methods:, Four candidate genes were selected a priori from two different steps in the oxidative stress pathway, specifically the synthesis of glutathione [catalytic subunit of glutamate cysteine ligase (GCLC) and regulatory subunit of glutamate cysteine ligase (GCLM)] and the removal of reactive oxygen species [superoxide dismutase 2 (SOD2) and glutathione peroxidase 3 (GPX3)]. Haplotype tagging and functional nucleotide polymorphisms were selected in each gene and tested for association with bipolar disorder under narrow (n = 240) and broad (n = 325) phenotypic models, compared to healthy controls (n = 392, comprising 166 psychiatrically assessed unaffected controls plus 226 healthy individuals). Results:, Single marker association analysis did not reveal significant association with bipolar disorder; however, haplotypes in the SOD2 gene showed nominal association (global ,2 = 8.94, p = 0.03; broad model). Interaction analysis revealed a significant interaction between SOD2 and GPX3 haplotypes, which further increases risk for bipolar disorder (odds ratio = 2.247, ,2 = 9.526, p = 0.002, corrected p = 0.029). Conclusions:, Further characterization of the SOD2 and GPX3 interaction using larger cohorts is required to determine the role of these oxidative pathway genes as risk factors for bipolar disorder. [source] | ||||||||||