Showing papers by "Mark Walker published in 2005"
TL;DR: This meta-analysis of case-control studies suggests that the factor V Leiden and prothrombin gene variant both confer an increased risk of giving birth to an intrauterine growth restricted infant, although this may be driven by small, poor-quality studies that demonstrated extreme associations.
127 citations
TL;DR: Using large-scale empirical and simulated data sets, it is found that the sample sizes used in the HapMap project are sufficient to capture common variation, but that performance declines substantially for variants with minor allele frequencies of <5%.
Abstract: A substantial investment has been made in the generation of large public resources designed to enable the identification of tag SNP sets, but data establishing the adequacy of the sample sizes used are limited. Using large-scale empirical and simulated data sets, we found that the sample sizes used in the HapMap project are sufficient to capture common variation, but that performance declines substantially for variants with minor allele frequencies of <5%.
112 citations
TL;DR: It is suggested that TFAP2B might be a new candidate for conferring susceptibility to type 2 diabetes and contribute to the pathogenesis of type 2 Diabetes mellitus.
Abstract: To search a gene(s) conferring susceptibility to type 2 diabetes mellitus, we genotyped nearly 60,000 gene-based SNPs for Japanese patients and found evidence that the gene at chromosome 6p12 encoding transcription-factor-activating protein 2β (TFAP2B) was a likely candidate in view of significant association of polymorphism in this gene with type 2 diabetes. Extensive analysis of this region identified that several variations within TFAP2B were significantly associated with type 2 diabetes [a variable number of tandem repeat locus: χ2=10.9, P=0.0009; odds ratio=1.57, 95% CI 1.20–2.06, intron 1+774 (G/T); χ2=11.6, P=0.0006; odds ratio=1.60, 95% CI 1.22–2.09, intron 1+2093 (A/C); χ2=12.2, P=0.0004; odds ratio=1.61, 95% CI 1.23–2.11]. The association of TFAP2B with type 2 diabetes was also observed in the UK population. These results suggest that TFAP2B might be a new candidate for conferring susceptibility to type 2 diabetes and contribute to the pathogenesis of type 2 diabetes.
76 citations
TL;DR: The risk of neonatal death and morbidity in second-born twins is higher in the group in which both twins were delivered vaginally and the groups in which the second twin was delivered by cesarean delivery after the first twin was delivery vaginally.
71 citations
TL;DR: It is demonstrated that self-reported smoking exposure during pregnancy is highly accurate and the high correlation coefficient suggests that this is a robust surrogate for cotinine levels.
67 citations
TL;DR: Genetic variation of the 16184-16193 poly-C tract is unlikely to have a major role in the cause of type 2 diabetes, and a meta-analysis of European studies confirmed this finding.
64 citations
TL;DR: The increased neonatal morbidity associated with PPROM appears to be inversely related to GA, and increased risk of chorioamnionitis is related to increased time to delivery.
Abstract: Objectives : To determine the prevalence of preterm prelabour rupture of the membranes (PP ROM) at Canadian university-affiliated perinatal referral centres, to assess the different management strategies, and to review neonatal outcomes. Methods : Twelve Canadian university-affiliated perinatal referral centres provided information on their management of PPROM, and 9 participated in data collection to determine prevalence. Ali women presenting with PPROM during a 2-week period were observed until delivery, and obstetric and neonatal outcome data were subsequently obtained. The total number of deliveries in each centre was recorded for the same ti me period. We also determined the incidence of PP ROM and the neonatal outcome for all women presenting with PPROM at the Kingston General Hospital from January 1999 to December 2001 by retrospective chart review. Results : In the 9 academic centres, 27 women (1 with a twin pregnancy) presented with PPROM during the 2-week period. There were 1168 deliveries during the same time period, giving a prevalence of PPROM of 2.3%. Overall, 53% of placentas submitted for histopathology after PPROM demonstrated evidence of chorioamnionitis. In the retrospective chart review, we found 153 cases of confirmed PPROM from January 1999 to December 2001, an incidence of 2.8%. Clinical management in ali centres was similar for most women who presented with PP ROM prior to 34 weeks' gestation. Management after 34 weeks' gestation varied among the 12 centres, ranging from immediate induction of labour to expectant management and induction at a greater gestational age (GA). Conclusions : The increased neonatal morbidity associated with PP ROM appears to be inversely related to GA increased risk of chorioamnionitis is related to increased time from PPROM to delivery.
59 citations
TL;DR: The linkage disequilibrium and haplotype structure across the HNF1alpha gene region using 29 single nucleotide polymorphisms (SNPs) was determined and no evidence of association between the tSNPs or haplotypes and type 2 diabetes was found.
Abstract: HNF1α (TCF1) is a key transcription factor that is essential for pancreatic β-cell development and function. Rare mutations of HNF1α cause maturity-onset diabetes of the young. A common variant, G319S, private to the Oji-Cree population, predisposes to type 2 diabetes, but the role of common HNF1α variation in European populations has not been comprehensively assessed. We determined the linkage disequilibrium and haplotype structure across the HNF1α gene region using 29 single nucleotide polymorphisms (SNPs). Eight tagging SNPs (tSNPs) that efficiently capture common haplotypes and the amino acid–changing variant, A98V, were genotyped in 5,307 subjects (2,010 type 2 diabetic case subjects, 1,643 control subjects, and 1,654 members of 521 families). We did not find any evidence of association between the tSNPs or haplotypes and type 2 diabetes. We could exclude odds ratios (ORs) >1.25 for all tSNPs. The rare V98 allele (∼3% frequency) showed possible evidence of association with type 2 diabetes (OR 1.23 [95% CI 0.99–1.54], P = 0.07), a result that was supported by meta-analysis of this and published studies (OR 1.31 [1.08–1.59], P = 0.007). Further studies are required to investigate this association, demonstrating the difficulty of defining the role of rare (
56 citations
TL;DR: Impaired pancreatic beta cell glucose sensing and whole-body insulin sensitivity predict progression to hyperglycaemia, override the importance of the clinical risk factors and highlight potential metabolic targets for prevention strategies.
Abstract: Aims/hypothesis
The aim of this prospective study was to investigate predictors of deteriorating glucose tolerance in subjects of British extraction.
53 citations
TL;DR: The present study, one of the largest association analyses yet reported at this locus, provides no evidence that the specific TNF or LTA variants examined influence susceptibility to type 2 diabetes.
Abstract: The proinflammatory cytokine TNF-α has been implicated in the pathogenesis of insulin resistance and type 2 diabetes, and variation in the gene encoding TNF-α (TNF) has shown inconsistent associations with susceptibility to both conditions. Additionally, the coding non-synonymous variant T60N in the neighbouring LTA gene has been reported to be associated with type 2 diabetes. The present study aimed to obtain a robust assessment of the role of variation in the tightly linked TNF/LTA region in diabetes susceptibility by genotyping TNF and LTA variants in large case-control resources. The G-308A and G-238A TNF promoter variants and the LTA T60N polymorphism were genotyped in two UK case samples that were ascertained for positive family history and/or early onset of type 2 diabetes (combined n=858) and in 1,257 ethnically matched controls. There were no significant associations between the T60N, G-308A or G-238A genotype and type 2 diabetes in the combined analysis (exact Cochran–Mantel–Haenszel statistic for ordered genotypes for T60N, p=0.69; for G-308A, p=0.51; for G-238A, p=0.16). The present study, one of the largest association analyses yet reported at this locus, provides no evidence that the specific TNF or LTA variants examined influence susceptibility to type 2 diabetes. More comprehensive studies of the TNF/LTA locus in substantially larger sample sets are required to establish whether genome sequence variation at this locus truly influences susceptibility to type 2 diabetes.
45 citations
TL;DR: The prevalence of birth weight discordance > or =25% among twin pregnancies was 8.6%, which is associated with lower gestational age at delivery and higher neonatal mortality rates, and may represent a pathologic process.
TL;DR: Cord prolapse, fetal distress, maternal complications, abnormal labor, and birth weight 25% larger than first twin were the most important predicators for operative deliveries.
TL;DR: Ethnic background is an independent predictor of periconceptional folic acid use among Canadian women in a multi-ethnic, urban setting and is more common among women of Jewish descent.
Abstract: Background : Randomized controlled trials have demonstrated that periconceptional folic acid supplementation has a dramatic effect in reducing neural tube defects, one of the most serious congenital anomalies. Unfortunately, supplementation tends to be suboptimal in disadvantaged populations. Objective : The primary objective was to determine patient factors associated with a lack of use of periconceptional folic acid among Canadian women in a multi-ethnic, urban setting. Our secondary objective was to assess patient knowledge about folic acid tablet supplementation and its link to reduced birth defects. Methods : We undertook a cross-sectional study to survey postpartum Toronto women on their use and knowledge of periconceptional folic acid. Results : Of the 383 women surveyed, only 28% took folic acid or a multivitamin containing folic acid during the periconceptional period. Multivariate analysis revealed that the use of periconceptional folic acid was more common among women of Jewish descent (adjusted relative risk [RR] 0.3; 95% confidence interval [Cl], 0.04-0.9) and those who had 1 or no children (adjusted RR 0.6; 95% Cl, 0.4-0:8). Not taking folic acid was associated with unplanned pregnancy (adjusted RR 1.5; 95% Cl, 1.4-1.6) and a lack of knowledge about when folic acid should be taken (adjusted RR 1.8; 95% Cl, 1.6-1.8). Conclusion : Ethnic background is an independent predictor of periconceptional folic acid use.
Journal Article•
TL;DR: It is concluded that the offspring of mothers with young-onset type 2 diabetes have a reduction in beta cell function, which is consistent with exposure to mild maternal hyperglycaemia programmingbeta cell function.
Abstract: Aims/hypothesis
Animal models indicate that even exposure to mild maternal hyperglycaemia in utero is detrimental to the beta cell function of the offspring, but evidence of this in humans is limited. In Europids who are diagnosed with type 2 diabetes before the age of 50 years, the risk of diabetes in the offspring of the diabetic mothers is greatly increased compared with the risk in those born to diabetic fathers. We hypothesised that offspring born to mothers with young-onset type 2 diabetes would have been exposed to mild hyperglycaemia in utero, so we studied the impact of this on their beta cell function.
TL;DR: Large, well‐characterized case‐control resources are made use of to enhance understanding of this susceptibility effect by examining related traits, such as body mass index (BMI), waist–hip ratio and age at diagnosis.
Abstract: Aims The Pro12Ala polymorphism in the PPARG gene alters amino acid sequence and has shown consistent association with susceptibility to Type 2 diabetes in several populations. The present study makes use of large, well-characterized case-control resources to enhance understanding of this susceptibility effect by examining related traits, such as body mass index (BMI), waist–hip ratio and age at diagnosis.
Methods The Pro12Ala variant was genotyped in two UK case samples, ascertained for positive family history and/or early onset of Type 2 diabetes (combined n = 971); and in 1257 ethnically matched control subjects.
Results There were significant associations of the Pro12Ala single nucleotide polymorphism (SNP) genotypes with diabetes in both case-control comparisons (P = 0.025 and P = 0.039). Comparing individuals homozygous for the Pro allele, with those carrying an Ala allele, the combined odds ratio for diabetes was 1.40 (95% CIs, 1.12–1.76, P = 0.0031). There was no association between the variant and either waist–hip ratio or age at diagnosis. Proline homozygosity was associated with increased BMI in one patient group (P = 0.013) and decreased BMI in the other (P = 0.038).
Conclusions This study confirms that variation within PPARG influences susceptibility to Type 2 diabetes in UK samples. However, the relationship between PPARG variation and BMI is more complex, and studies in much larger sample sets will be required to more precisely characterize the effect of this variant on adiposity.
TL;DR: These studies confirm calpain 10 expression in cultured human muscle cells and support a role for calpains in insulin-stimulated glucose uptake in human skeletal muscle cells that may be relevant to the pathogenesis of the peripheral insulin resistance in type 2 diabetes.
TL;DR: In early November 2005, an increase in cases of cryptosporidiosis was noted in the two counties of Gwynedd and Anglesey in northwest Wales.
Abstract: In early November 2005, an increase in cases of cryptosporidiosis was noted in the two counties of Gwynedd and Anglesey in northwest Wales in the United Kingdom
TL;DR: The reported methods of SGA prediction are not satisfactory because the diagnostic performance is poor and the interval between prediction and delivery is too short.
Abstract: Background: Small for gestational age (SGA) is one of the major determinants of perinatal mortality and morbidity, and may relate in adult diseases. Early prediction of SGA could be helpful for health care providers and public health workers in guiding antenatal management and prevention. The reported methods of SGA prediction are not satisfactory because the diagnostic performance is poor and the interval between prediction and delivery is too short.
Aims: To establish a SGA prediction model for twin pregnancies based on variables obtainable in early gestation.
Methods: We used a large twin registry United States data (1995–1997). The study subjects were randomly divided into two groups: group 1 to establish the prediction model by logistic regression and group 2 to validate the prediction model. SGA was defined as birth weight for gestational age z scores less than 10th percentiles. Pair of twin was the unit of analysis. Two sets of multiple logistic regression analyses with different outcome measures – one or both twins SGAs and both twins SGAs – were used to establish the prediction model.
Results: The sensitivity, specificity, and positive predictive value were 52.3, 62.5, and 21.5%, respectively, at the cutoff value 0.16 in a SGA prediction model based on maternal race, education, marital status, parity, prenatal care visit initiation, cigarette smoking, and paternal race.
Conclusions: A prediction model based on determinants that can be obtained at early gestation might be useful in the management of pregnancies with high risk of SGA in twins.
TL;DR: Analysis of the literature revealed that a major mechanism of folic acid in improving infant health may be related to its effect in correcting maternal folate-homocysteine-methylenetetrahydrofolate reductase metabolic defects.
Abstract: Objectives : First, to examine the biological basis of why folic acid may have health effects beyond its proven effect of reducing neural tube defects; and second, to explore current controversial policies of folic acid supplementation and food fortification. Methods : We searched MEDLINE for English-language papers published from 1991 to 2003, using the key words "folic acid" and "folate." The literature search was restricted to human studies. Of 8986 publications identified, 65 were relevant to the objectives of this paper. Results : Analysis of the literature revealed that a major mechanism of folic acid in improving infant health may be related to its effect in correcting maternal folate-homocysteine-methylenetetrahydrofolate reductase metabolic defects. Conversely, exposure to high levels of folic acid may have such adverse health effects as increased risk of neurologic disorders in the general population. Conclusions : Randomized trials or well-designed prospective cohort studies are needed to assess the effects of folic acid on various pregnancy outcomes. To enable an examination of the association between folic acid and rare outcomes, such as a specific category of birth defects and fetal and neonatal deaths, it is necessary to recruit a large number of pregnant women to participate in such studies.
TL;DR: HASTE sequence provides the grey-white matter differentiation that is necessary to make the diagnosis of grey-matter-lined schizencephaly clefts and can provide information regarding other commonly associated anatomic anomalies.
Abstract: Background: Schizencephaty is a brain anomaly that can be associated with severe neonatal morbidity and mortality. Precise antenatal diagnosis is critical to help families make a decision regarding the continuation of pregnancy. A sequence of magnetic resonance imaging MRI called HASTE (Half-Fourier Acquisition Single-Shot Turbo Spin-Echo) has been used Prenatally for this purpose. Case: We used an additional MRI sequence called true-FISP (True Fast Imaging with Steady-State Precession) to diagnose schizencephaly in a 15-year-old primigravid woman. This sequence has not been previously described m prenatal MRI. Conclusion: HASTE sequence provides the grey-white matter differentiation that is necessary to make the diagnosis of grey-matter-lined schizencephaly clefts. True-FISP sequence has potentially higher resolution images because it is not prone to blurring of edges and is less sensitive to flowing fluid movement. Using these two MRI sequences is essential for confirming the diagnosis of schizencephaty and can provide information regarding other commonly associated anatomic anomalies.