Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Raj Ramesar is active.

Publication


Featured researches published by Raj Ramesar.


The Lancet | 2011

Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial

John Burn; Anne-Marie Gerdes; Finlay Macrae; Jukka Pekka Mecklin; Gabriela Moeslein; Sylviane Olschwang; D. Eccles; D. Gareth Evans; Eamonn R. Maher; Lucio Bertario; Marie Luise Bisgaard; Malcolm G. Dunlop; Judy W. C. Ho; Shirley Hodgson; Annika Lindblom; Jan Lubinski; Patrick J. Morrison; Victoria Murday; Raj Ramesar; Lucy Side; Rodney J. Scott; Huw Thomas; Hans F. A. Vasen; Gail Barker; Gillian Crawford; Faye Elliott; Mohammad Movahedi; Kirsi Pylvänäinen; Juul T. Wijnen; Riccardo Fodde

Summary Background Observational studies report reduced colorectal cancer in regular aspirin consumers. Randomised controlled trials have shown reduced risk of adenomas but none have employed prevention of colorectal cancer as a primary endpoint. The CAPP2 trial aimed to investigate the antineoplastic effects of aspirin and a resistant starch in carriers of Lynch syndrome, the major form of hereditary colorectal cancer; we now report long-term follow-up of participants randomly assigned to aspirin or placebo. Methods In the CAPP2 randomised trial, carriers of Lynch syndrome were randomly assigned in a two-by-two factorial design to 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was in blocks of 16 with provision for optional single-agent randomisation and extended postintervention double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. This trial is registered, ISRCTN59521990. Results 861 participants were randomly assigned to aspirin or aspirin placebo. At a mean follow-up of 55·7 months, 48 participants had developed 53 primary colorectal cancers (18 of 427 randomly assigned to aspirin, 30 of 434 to aspirin placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 0·63 (95% CI 0·35–1·13, p=0·12). Poisson regression taking account of multiple primary events gave an incidence rate ratio (IRR) of 0·56 (95% CI 0·32–0·99, p=0·05). For participants completing 2 years of intervention (258 aspirin, 250 aspirin placebo), per-protocol analysis yielded an HR of 0·41 (0·19–0·86, p=0·02) and an IRR of 0·37 (0·18–0·78, p=0·008). No data for adverse events were available postintervention; during the intervention, adverse events did not differ between aspirin and placebo groups. Interpretation 600 mg aspirin per day for a mean of 25 months substantially reduced cancer incidence after 55·7 months in carriers of hereditary colorectal cancer. Further studies are needed to establish the optimum dose and duration of aspirin treatment. Funding European Union; Cancer Research UK; Bayer Corporation; National Starch and Chemical Co; UK Medical Research Council; Newcastle Hospitals trustees; Cancer Council of Victoria Australia; THRIPP South Africa; The Finnish Cancer Foundation; SIAK Switzerland; Bayer Pharma.


The New England Journal of Medicine | 2008

Effect of Aspirin or Resistant Starch on Colorectal Neoplasia in the Lynch Syndrome

John Burn; D. Timothy Bishop; Jukka Pekka Mecklin; Finlay Macrae; Gabriela Möslein; Sylviane Olschwang; Marie Luise Bisgaard; Raj Ramesar; Diana Eccles; Eamonn R. Maher; Lucio Bertario; Heikki Järvinen; Annika Lindblom; D. Gareth Evans; Jan Lubinski; Patrick Morrison; Judy W. C. Ho; Hans F. A. Vasen; Lucy Side; Huw Thomas; Rodney J. Scott; Malcolm G. Dunlop; Gail Barker; Faye Elliott; Jeremy R. Jass; Ricardo Fodde; Henry T. Lynch; John C. Mathers

BACKGROUND Observational and epidemiologic data indicate that the use of aspirin reduces the risk of colorectal neoplasia; however, the effects of aspirin in the Lynch syndrome (hereditary nonpolyposis colon cancer) are not known. Resistant starch has been associated with an antineoplastic effect on the colon. METHODS In a randomized, placebo-controlled trial, we used a two-by-two design to investigate the effects of aspirin, at a dose of 600 mg per day, and resistant starch (Novelose), at a dose of 30 g per day, in reducing the risk of adenoma and carcinoma among persons with the Lynch syndrome. RESULTS Among 1071 persons in 43 centers, 62 were ineligible to participate in the study, 72 did not enter the study, and 191 withdrew from the study. These three categories were equally distributed across the study groups. Over a mean period of 29 months (range, 7 to 74), colonic adenoma or carcinoma developed in 141 participants. Of 693 participants randomly assigned to receive aspirin or placebo, neoplasia developed in 66 participants receiving aspirin (18.9%), as compared with 65 receiving placebo (19.0%) (relative risk, 1.0; 95% confidence interval [CI], 0.7 to 1.4). There were no significant differences between the two groups with respect to the development of advanced neoplasia (7.4% and 9.9%, respectively; P=0.33). Among the 727 participants receiving resistant starch or placebo, neoplasia developed in 67 participants receiving starch (18.7%), as compared with 68 receiving placebo (18.4%) (relative risk, 1.0; 95% CI, 0.7 to 1.4). Advanced adenomas and colorectal cancers were evenly distributed in the two groups. The prevalence of serious adverse events was low, and the events were evenly distributed. CONCLUSIONS The use of aspirin, resistant starch, or both for up to 4 years has no effect on the incidence of colorectal adenoma or carcinoma among carriers of the Lynch syndrome. (Current Controlled Trials number, ISRCTN59521990.)


Journal of Molecular Medicine | 2000

Mutations of the gene encoding the transmembrane transporter protein ABC-C6 cause pseudoxanthoma elasticum

Berthold Struk; Li Cai; Stéphanie Zäch; Wan Ji; Joon Chung; Amanda L. Lumsden; Markus Stumm; Marcel Huber; Lori Schaen; Chung-Ah Kim; Lowell A. Goldsmith; Denis Viljoen; Luis E. Figuera; Wayne Fuchs; Francis L. Munier; Raj Ramesar; Daniel Hohl; Robert I. Richards; Kenneth H. Neldner; Klaus Lindpaintner

Abstract. We recently published the precise chromosomal localization on chromosome 16p13.1 of the genetic defect underlying pseudoxanthoma elasticum (PXE), an inherited disorder characterized by progressive calcification of elastic fibers in skin, eye, and the cardiovascular system. Here we report the identification of mutations in the gene encoding the transmembrane transporter protein, ABC-C6 (also known as MRP-6), one of the four genes located in the region of linkage, as cause of the disease. Sequence analysis in four independent consanguineous families from Switzerland, Mexico, and South Africa and in one non-consanguineous family from the United States demonstrated several different mis-sense mutations to cosegregate with the disease phenotype. These findings are consistent with the conclusion that PXE is a recessive disorder that displays allelic heterogeneity, which may explain the considerable phenotypic variance characteristic of the disorder.


American Journal of Human Genetics | 2000

Genetic Heterogeneity of Usher Syndrome: Analysis of 151 Families with Usher Type I

Lisa M. Astuto; Michael D. Weston; Carol Carney; Denise M. Hoover; C.W.R.J. Cremers; M. Wagenaar; Claes Möller; Richard J.H. Smith; Sandra Pieke-Dahl; Jacquie Greenberg; Raj Ramesar; Samuel G. Jacobson; Carmen Ayuso; John R. Heckenlively; Marta L Tamayo; Michael B. Gorin; Willie Reardon; William J. Kimberling

Usher syndrome type I is an autosomal recessive disorder marked by hearing loss, vestibular areflexia, and retinitis pigmentosa. Six Usher I genetic subtypes at loci USH1A-USH1F have been reported. The MYO7A gene is responsible for USH1B, the most common subtype. In our analysis, 151 families with Usher I were screened by linkage and mutation analysis. MYO7A mutations were identified in 64 families with Usher I. Of the remaining 87 families, who were negative for MYO7A mutations, 54 were informative for linkage analysis and were screened with the remaining USH1 loci markers. Results of linkage and heterogeneity analyses showed no evidence of Usher types Ia or Ie. However, one maximum LOD score was observed lying within the USH1D region. Two lesser peak LOD scores were observed outside and between the putative regions for USH1D and USH1F, on chromosome 10. A HOMOG chi(2)((1)) plot shows evidence of heterogeneity across the USH1D, USH1F, and intervening regions. These results provide conclusive evidence that the second-most-common subtype of Usher I is due to genes on chromosome 10, and they confirm the existence of one Usher I gene in the previously defined USH1D region, as well as providing evidence for a second, and possibly a third, gene in the 10p/q region.


Lancet Oncology | 2012

Long-term effect of resistant starch on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial.

John C. Mathers; Mohammad Movahedi; Finlay Macrae; Jukka Pekka Mecklin; Gabriela Moeslein; Sylviane Olschwang; Diana Eccles; Gareth Evans; Eamonn R. Maher; Lucio Bertario; Marie Luise Bisgaard; Malcolm G. Dunlop; Judy W. C. Ho; Shirley Hodgson; Annika Lindblom; Jan Lubinski; Patrick J. Morrison; Victoria Murday; Raj Ramesar; Lucy Side; Rodney J. Scott; Huw Thomas; Hans F. A. Vasen; Anne-Marie Gerdes; Gail Barker; Gillian Crawford; Faye Elliott; Kirsi Pylvänäinen; Juul T. Wijnen; Riccardo Fodde

BACKGROUND Observational studies report that higher intake of dietary fibre (a heterogeneous mix including non-starch polysaccharides and resistant starches) is associated with reduced risk of colorectal cancer, but no randomised trials with prevention of colorectal cancer as a primary endpoint have been done. We assessed the effect of resistant starch on the incidence of colorectal cancer. METHODS In the CAPP2 study, individuals with Lynch syndrome were randomly assigned in a two-by-two factorial design to receive 600 mg aspirin or aspirin placebo or 30 g resistant starch or starch placebo, for up to 4 years. Randomisation was done with a block size of 16. Post-intervention, patients entered into double-blind follow-up; participants and investigators were masked to treatment allocation. The primary endpoint for this analysis was development of colorectal cancer in participants randomly assigned to resistant starch or resistant-starch placebo with both intention-to-treat and per-protocol analyses. This study is registered, ISRCTN 59521990. FINDINGS 463 patients were randomly assigned to receive resistant starch and 455 to receive resistant-starch placebo. At a median follow-up 52·7 months (IQR 28·9-78·4), 53 participants developed 61 primary colorectal cancers (27 of 463 participants randomly assigned to resistant starch, 26 of 455 participants assigned to resistant-starch placebo). Intention-to-treat analysis of time to first colorectal cancer showed a hazard ratio (HR) of 1·40 (95% CI 0·78-2·56; p=0·26) and Poisson regression accounting for multiple primary events gave an incidence rate ratio (IRR) of 1·15 (95% CI 0·66-2·00; p=0·61). For those completing 2 years of intervention, per-protocol analysis yielded a HR of 1·09 (0·55-2·19, p=0·80) and an IRR of 0·98 (0·51-1·88, p=0·95). No information on adverse events was gathered during post-intervention follow-up. INTERPRETATION Resistant starch had no detectable effect on cancer development in carriers of hereditary colorectal cancer. Dietary supplementation with resistant starch does not emulate the apparently protective effect of diets rich in dietary fibre against colorectal cancer. FUNDING European Union, Cancer Research UK, Bayer Corporation, National Starch and Chemical Co, UK Medical Research Council, Newcastle Hospitals Trustees, Cancer Council of Victoria Australia, THRIPP South Africa, The Finnish Cancer Foundation, SIAK Switzerland, and Bayer Pharma.


Journal of Molecular Medicine | 2001

A novel Q378X mutation exists in the transmembrane transporter protein ABCC6 and its pseudogene : implications for mutation analysis in pseudoxanthoma elasticum

Li Cai; Amanda L. Lumsden; Ulf P. Guenther; Sarah A. Neldner; Stéphanie Zäch; Hans Knoblauch; Raj Ramesar; Daniel Hohl; David F. Callen; Kenneth H. Neldner; Klaus Lindpaintner; Robert I. Richards; Berthold Struk

Pseudoxanthoma elasticum (PXE) is an inherited disorder of the elastic tissue with characteristic progressive calcification of elastic fibers in skin, eye, and the cardiovascular system. Recently mutations in the ABCC6 gene, encoding a transmembrane transporter protein, were identified as cause of the disease. Surprisingly, sequence and RFLP analysis for exon 9 with primers corresponding to flanking intronic sequence in diseased and haplotype negative members from all of our families and in a control population revealed either a homozygous or heterozygous state for the Q378X (1132C→T) nonsense mutation in all individuals. With the publication of the genomic structure of the PXE locus we had identified the starting point of a large genomic segmental duplication within the locus in the cytogenetic interval defined by the Cy19 and Cy185 somatic cell hybrid breakpoints on chromosome 16p13.1. By means of somatic cell hybrid mapping we located this starting point telomeric to exon 10 of ABCC6. The duplication, however, does not include exon 10, but exons 1–9. These findings suggest that one or several copies of an ABCC6 pseudogene (ψABCC6) lie within this large segmental duplication. At least one copy contains exons 1–9 and maps to the chromosomal interval defined by the Cy163 and Cy11 breakpoints. Either this copy and/or an additional copy of ψABCC6 within Cy19-Cy183 carries the Q378X mutation that masks the correct identification of this nonsense mutation as being causative in pseudoxanthoma elasticum. Long-range PCR of exon 9 starting from sequence outside the genomic replication circumvents interference from the ψABCC6 DNA sequences and demonstrates that the Q378X mutation in the ABCC6 gene is associated with PXE in some families. These findings lead us to propose that gene conversion mechanisms from ψABCC6 to ABCC6 play a functional role in mutations causing PXE.


PLOS ONE | 2014

Association of Variants at BCL11A and HBS1L-MYB with Hemoglobin F and Hospitalization Rates among Sickle Cell Patients in Cameroon

Ambroise Wonkam; Valentina Josiane Ngo Bitoungui; Anna Alvera Vorster; Raj Ramesar; Richard S. Cooper; Bamidele O. Tayo; Guillaume Lettre; Jeanne Ngogang

Background Genetic variation at loci influencing adult levels of HbF have been shown to modify the clinical course of sickle cell disease (SCD). Data on this important aspect of SCD have not yet been reported from West Africa. We investigated the relationship between HbF levels and the relevant genetic loci in 610 patients with SCD (98% HbSS homozygotes) from Cameroon, and compared the results to a well-characterized African-American cohort. Methods and Findings Socio-demographic and clinical features were collected and medical records reviewed. Only patients >5 years old, who had not received a blood transfusion or treatment with hydroxyurea were included. Hemoglobin electrophoresis and a full blood count were conducted upon arrival at the hospital. RFLP-PCR was used to describe the HBB gene haplotypes. SNaPshot PCR, Capillary electrophoresis and cycle sequencing were used for the genotyping of 10 selected SNPs. Genetic analysis was performed with PLINK software and statistical models in the statistical package R. Allele frequencies of relevant variants at BCL11A were similar to those detected in African Americans; although the relationships with Hb F were significant (p <.001), they explained substantially less of the variance in HbF than was observed among African Americans (∼ 2% vs 10%). SNPs in HBS1L-MYB region (HMIP) likewise had a significant impact on HbF, however, we did not find an association between HbF and the variations in HBB cluster and OR51B5/6 locus on chromosome 11p, due in part to the virtual absence of the Senegal and Indian Arab haplotypes. We also found evidence that selected SNPs in HBS1L-MYB region (HMIP) and BCL11A affect both other hematological indices and rates of hospitalization. Conclusions This study has confirmed the associations of SNPs in BCL11A and HBS1L-MYB and fetal haemoglobin in Cameroonian SCA patients; hematological indices and hospitalization rates were also associated with specific allelic variants.


Human Mutation | 2010

How to catch all those mutations--the report of the third Human Variome Project Meeting, UNESCO Paris, May 2010.

Maija Kohonen-Corish; Jumana Y. Al-Aama; Arleen D. Auerbach; Myles Axton; Carol Isaacson Barash; Inge Bernstein; Christophe Béroud; John Burn; Fiona Cunningham; Garry R. Cutting; Johan T. den Dunnen; Marc S. Greenblatt; Jim Kaput; Michael Katz; Annika Lindblom; Finlay Macrae; Donna Maglott; Gabriela Möslein; Sue Povey; Raj Ramesar; Sue Richards; Daniela Seminara; María Jesús Sobrido; Sean V. Tavtigian; Graham R. Taylor; Mauno Vihinen; Ingrid Winship; Richard G.H. Cotton

The third Human Variome Project (HVP) Meeting “Integration and Implementation” was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10–14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health. The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current framework of HVP activities: Ethics; Nomenclature and Standards; Publication, Credit and Incentives; Data Collection from Clinics; Overall Data Integration and Access—Peripheral Systems/Software; Data Collection from Laboratories; Assessment of Pathogenicity; Country Specific Collection; Translation to Healthcare and Personalized Medicine; Data Transfer, Databasing, and Curation; Overall Data Integration and Access—Central Systems; and Funding Mechanisms and Sustainability. In addition, three societies that support the goals and the mission of HVP also held their own Workshops with the view to advance disease‐specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium. Hum Mutat 71:1374–1381, 2010.


Nature Reviews Genetics | 2008

South Africa: from species cradle to genomic applications

Billie-Jo Hardy; Béatrice Séguin; Raj Ramesar; Peter Singer; Abdallah S. Daar

The South African government is committed to science and technology innovation, to establishing a knowledge-based economy and to harnessing life-sciences research for health and economic development. Given the constraints and the early stage of development of the field as a whole in South Africa, we found an impressive amount of research on human genomic variation in this country. Encouragingly, South Africa is beginning to apply genomics to address local health needs, including HIV and tuberculosis (TB) infections. We document a number of initiatives in South Africa that are beginning to study genetic variation within the various local indigenous populations. Other early initiatives focus on pharmacogenetic studies, mutation characterization in individual disease genes and genome-wide association studies. Public engagement in genomic issues is spear-headed by The Africa Genome Education Institute.


Journal of Affective Disorders | 2014

Relationship between sunlight and the age of onset of bipolar disorder: an international multisite study.

Michael Bauer; Tasha Glenn; Martin Alda; Ole A. Andreassen; Elias Angelopoulos; Raffaella Ardau; Christopher Baethge; Rita Bauer; Frank Bellivier; R.H. Belmaker; Michael Berk; Thomas Bjella; Letizia Bossini; Yuly Bersudsky; Eric Yat Wo Cheung; Jörn Conell; Maria Del Zompo; Seetal Dodd; Bruno Etain; Andrea Fagiolini; Mark A. Frye; Kostas N. Fountoulakis; Jade Garneau-Fournier; Ana González-Pinto; Hirohiko Harima; Stefanie Hassel; Chantal Henry; Apostolos Iacovides; Erkki Isometsä; Flávio Kapczinski

BACKGROUND The onset of bipolar disorder is influenced by the interaction of genetic and environmental factors. We previously found that a large increase in sunlight in springtime was associated with a lower age of onset. This study extends this analysis with more collection sites at diverse locations, and includes family history and polarity of first episode. METHODS Data from 4037 patients with bipolar I disorder were collected at 36 collection sites in 23 countries at latitudes spanning 3.2 north (N) to 63.4 N and 38.2 south (S) of the equator. The age of onset of the first episode, onset location, family history of mood disorders, and polarity of first episode were obtained retrospectively, from patient records and/or direct interview. Solar insolation data were obtained for the onset locations. RESULTS There was a large, significant inverse relationship between maximum monthly increase in solar insolation and age of onset, controlling for the country median age and the birth cohort. The effect was reduced by half if there was no family history. The maximum monthly increase in solar insolation occurred in springtime. The effect was one-third smaller for initial episodes of mania than depression. The largest maximum monthly increase in solar insolation occurred in northern latitudes such as Oslo, Norway, and warm and dry areas such as Los Angeles, California. LIMITATIONS Recall bias for onset and family history data. CONCLUSIONS A large springtime increase in sunlight may have an important influence on the onset of bipolar disorder, especially in those with a family history of mood disorders.

Collaboration


Dive into the Raj Ramesar's collaboration.

Top Co-Authors

Avatar
Top Co-Authors

Avatar

Dan J. Stein

University of Cape Town

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Lisa Roberts

University of Cape Town

View shared research outputs
Top Co-Authors

Avatar

Michele Ramsay

University of the Witwatersrand

View shared research outputs
Top Co-Authors

Avatar
Top Co-Authors

Avatar

Finlay Macrae

Royal Melbourne Hospital

View shared research outputs
Researchain Logo
Decentralizing Knowledge