Beverley Burke - Academia.edu (original) (raw)

Papers by Beverley Burke

Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer this process is available in the click Request Permissions in the middle column of the Web page under Services. Further information about Office. Once the online version of the published article for which permission is being requested is located, can be obtained via RightsLink, a service of the Copyright Clearance Center, not the EditorialHypertensionin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on March 6,

Circulation: Cardiovascular Genetics, 2013

Background— Blood pressure (BP) responses to dietary sodium and potassium intervention and cold p... more Background— Blood pressure (BP) responses to dietary sodium and potassium intervention and cold pressor test vary considerably among individuals. We aimed to identify novel genetic variants influencing individuals’ BP responses to dietary intervention and cold pressor test. Methods and Results— We conducted a genome-wide association study of BP responses in 1881 Han Chinese and de novo genotyped top findings in 698 Han Chinese. Diet-feeding study included a 7-day low-sodium (51.3 mmol/d), a 7-day high-sodium (307.8 mmol/d), and a 7-day high-sodium plus potassium supplementation (60 mmol/d). Nine BP measurements were obtained during baseline observation and each intervention period. The meta-analyses identified 8 novel loci for BP phenotypes, which physically mapped in or near PRMT6 ( P =7.29×10 –9 ), CDCA7 ( P =3.57×10 –8 ), PIBF1 ( P =1.78×10 –9 ), ARL4C ( P =1.86×10 –8 ), IRAK1BP1 ( P =1.44×10 −10 ), SALL1 ( P =7.01×10 –13 ), TRPM8 ( P =2.68×10 –8 ), and FBXL13 ( P =3.74×10 –9 ). ...

Hypertension, 2006

Human hypertension arises from a combination of genetic factors and lifestyle influences. With ca... more Human hypertension arises from a combination of genetic factors and lifestyle influences. With cardiovascular disease set to become the number 1 cause of death worldwide, it is important to understand the etiologic mechanisms for hypertension, because these might provide new routes to improved treatment. The British Genetics of Hypertension Study has recently published a primary genome screen that identified 4 chromosomal regions of interest. We have now genotyped additional markers to confirm the most promising regions for follow-up studies. Thirty-four additional microsatellites were genotyped in our severely hypertensive affected sibling pair resource (now 1635 families with 2142 affected sibling pairs), leading to a substantial increase in information content in the regions of interest. We found increased support for linkage of chromosome 5q13 to human hypertension (multipoint logarithm of odds=2.50) with 3 adjacent markers yielding single point logarithm of odds scores of 3.22,...

The American Journal of Human Genetics, 2006

Identification of the genetic influences on human essential hypertension and other complex diseas... more Identification of the genetic influences on human essential hypertension and other complex diseases has proved difficult, partly because of genetic heterogeneity. In many complex-trait resources, additional phenotypic data have been collected, allowing comorbid intermediary phenotypes to be used to characterize more genetically homogeneous subsets. The traditional approach to analyzing covariate-defined subsets has typically depended on researchers' previous expectations for definition of a comorbid subset and leads to smaller data sets, with a concomitant attrition in power. An alternative is to test for dependence between genetic sharing and covariates across the entire data set. This approach offers the advantage of exploiting the full data set and could be widely applied to complex-trait genome scans. However, existing maximum-likelihood methods can be prohibitively computationally expensive, especially since permutation is often required to determine significance. We developed a less computationally intensive score test and applied it to biometric and biochemical covariate data, from 2,044 sibling pairs with severe hypertension, collected by the British Genetics of Hypertension (BRIGHT) study. We found genomewide-significant evidence for linkage with hypertension and several related covariates. The strongest signals were with leaner-body-mass measures on chromosome 20q (maximum) and with parameters of renal function on chromosome 5p (maximum). After correction for LOD p 4.24 LOD p 3.71 the multiple traits and genetic locations studied, our global genomewide P value was .046. This is the first identity-bydescent regression analysis of hypertension to our knowledge, and it demonstrates the value of this approach for the incorporation of additional phenotypic information in genetic studies of complex traits.

PloS one, 2009

WNK1--a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) contr... more WNK1--a serine/threonine kinase involved in electrolyte homeostasis and blood pressure (BP) control--is an excellent candidate gene for essential hypertension (EH). We and others have previously reported association between WNK1 and BP variation. Using tag SNPs (tSNPs) that capture 100% of common WNK1 variation in HapMap, we aimed to replicate our findings with BP and to test for association with phenotypes relating to WNK1 function in the British Genetics of Hypertension (BRIGHT) study case-control resource (1700 hypertensive cases and 1700 normotensive controls). We found multiple variants to be associated with systolic blood pressure, SBP (7/28 tSNPs min-p = 0.0005), diastolic blood pressure, DBP (7/28 tSNPs min-p = 0.002) and 24 hour urinary potassium excretion (10/28 tSNPs min-p = 0.0004). Associations with SBP and urine potassium remained significant after correction for multiple testing (p = 0.02 and p = 0.01 respectively). The major allele (A) of rs765250, located in intron ...

Journal of Clinical Pathology, 2003

Background: The immune system has been implicated in the pathogenesis of certain clinical manifes... more Background: The immune system has been implicated in the pathogenesis of certain clinical manifestations of parvovirus B19 infection, including rash and arthralgia. Cytokines feature in the pathogenesis of parvovirus B19 infection, so inherited variability in cytokine responses to B19 infection might have a bearing on the symptomatology of parvovirus B19 infection. Aims: To investigate the possible role of cytokine gene polymorphisms in the clinical manifestations of parvovirus B19 infection. Methods: Thirty six patients with a variety of symptoms at acute infection and follow up (mean, 22.0 months) and controls (99-330, depending on the locus) were examined for the following cytokine polymorphisms: tumour necrosis factor α (TNFα), −308; interferon γ (IFN-γ), +874; interleukin 6 (IL-6), −174; IL-10, −592, −819, and −1082; and transforming growth factor β1 (TGFβ1), +869 (codon 10) and +915 (codon 25). Results: The TNFα −308*A allele occurred in 13.9% of the parvovirus group compared with 27.0% of the control group (odds ratio (OR), 0.44; p = 0.02). The TGFβ1 CG/CG haplotype was more frequent in the parvovirus group than in the controls (16.7% v 5%; OR, 4.8; p = 0.02). Within the B19 infected group, the TGFβ1 +869 T allele was associated with skin rash at acute infection (p = 0.005), whereas at follow up the IFN-γ +874 T allele was associated with the development of anti-B19 non-structural protein 1 antibodies (p = 0.04). Conclusions: The results of the present study suggest that inherited variability in cytokine responses may affect the likelihood of developing symptoms during parvovirus infection.

Seminars in Nephrology, 2002

Monogenic or Mendelian forms of hypertension have ushered in a revolution in our knowledge. If we... more Monogenic or Mendelian forms of hypertension have ushered in a revolution in our knowledge. If we add information on syndromes involving low blood pressure, this knowledge base is doubled. Glucocorticoid-remediable aldosteronism, apparent mineralocorticoid excess, and mutations in the mineralocorticoid receptor gene have given us brilliant insights into mineralocorticoid-induced hypertension. The latter discovery has elucidated how mutations may modify the receptor sufficiently to allow erstwhile antagonists to have an agonistic action. The epithelial sodium channel (ENaC) has been elucidated. Gain-of-function mutations in the beta and gamma subunits of ENaC cause Liddle&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. Loss-of-function mutations in all 3 subunits of ENaC cause hypotension (pseudohypoaldosteronism type I). Thus, all 3 subunits can be mutated, causing either hyper- or hypotension. Three loci have been described for Gordon&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome, pseudohypoaldosteronism type II; 2 members of the WNK (with no ly sine K) serine-threonine kinase family have recently been found to be responsible. Autosomal-dominant hypertension with brachydactyly features normal sodium and renin-angiotensin-aldosterone responses. The gene has been mapped to chromosome 12p. The condition is interesting because it may represent a novel neural form of hypertension. The elucidation of Mendelian blood pressure-regulatory disorders has been a resounding success.

The Journal of Infectious Diseases, 2008

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathoge... more Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a multisystem disease, the pathogenesis of which remains undetermined. We set out to determine the precise abnormalities of gene expression in the blood of patients with CFS/ME. We analyzed gene expression in peripheral blood from 25 patients with CFS/ME diagnosed according to the Centers for Disease Control and Prevention diagnostic criteria and 50 healthy blood donors, using a microarray with a cutoff fold difference of expression of 2.5. Genes showing differential expression were further analyzed in 55 patients with CFS/ME and 75 healthy blood donors, using quantitative polymerase chain reaction. Differential expression was confirmed for 88 genes; 85 were upregulated, and 3 were downregulated. Highly represented functions were hematological disease and function, immunological disease and function, cancer, cell death, immune response, and infection. Clustering of quantitative polymerase chain reaction data from patients with CFS/ME revealed 7 subtypes with distinct differences in Medical Outcomes Survey Short Form-36 scores, clinical phenotypes, and severity.

Gynecologic Oncology, 2006

Previous studies have identified loss of chromosomal regions 7p12-q11.2 and 8p12-p21 in choriocar... more Previous studies have identified loss of chromosomal regions 7p12-q11.2 and 8p12-p21 in choriocarcinoma suggesting that suppressor genes involved in tumour development may be located within these regions. Our objectives were to refine the regions of loss and evaluate these deletions as prognostic indicators of trophoblastic tumour development following molar pregnancy. Fluorescent microsatellite genotyping was used to perform deletion mapping in a series of thirty-nine gestational trophoblastic tumours (GTT) including both choriocarcinoma and placental site trophoblastic tumours. Significant loss of heterozygosity (LOH) was found for both regions in GTT that originated in non-molar pregnancies. Although no common interval of loss was found in those GTT with LOH for the 7q11.2 region, for the 8p12-p21 locus, markers D8S1731 and NEFL defined a minimal region of loss in all tumours showing LOH. However, complete LOH of either region occurred in only a minority of tumours (20%; chromosome 7: 24%; chromosome 8) suggesting that loss of neither region is likely to be a primary event in the development of GTT. This was further supported by the observation that no deletions were found in either region for the fourteen GTT that followed complete molar pregnancies. While we have defined a minimal interval in 8p12-p21 in which tumour suppressor genes involved in GTT are likely to be located, the data suggest that deletions in 7q11.2 or 8p12-p21 are unlikely to be useful prognostic indicators in the management of patients with molar pregnancies.

Background: Inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) is a negative regulator of ... more Background: Inositol polyphosphate phosphatase-like 1 (INPPL1, SHIP2) is a negative regulator of insulin signalling and has previously been found to be associated with hypertension, obesity and type 2 diabetes in a cohort of families with diabetes in the UK presenting features of metabolic syndrome. In particular, a haplotype of three genetic polymorphisms (rs2276047, rs9886 and an insertion/deletion polymorphism in intron 1) was found to be strongly associated with increased susceptibility to hypertension. Objective and methods: To assess if INPPL1 variants play a direct role in the development of essential hypertension, we genotyped the three previously associated INPPL1 polymorphisms in a cohort of 712 families with severe hypertension from the BRIGHT study transmission disequilibrium test cohort. Results: We found no evidence of significant association between hypertension and any of the three INPPL1 polymorphisms or haplotypes (p.0.1). Conclusion: These results suggest that INPPL1 variants may be involved in mechanisms causing hypertension in metabolic syndrome patients specifically.

Nature Genetics, 2007

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MH... more We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major…