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Voltage-gated calcium channels have been implicated in schizophrenia aetiology; however, little is known about their involvement in antipsychotic treatment response. This study investigated variants within the calcium channel subunit genes for association with antipsychotic treatment response in a first episode schizophrenia cohort. Twelve regulatory variants within seven genes were shown to be significantly associated with treatment outcome. Most notably, the CACNA1B rs2229949 CC genotype was associated with improved negative symptomology, where the C allele was predicted to abolish a miRNA-binding site (has-mir-5002-3p), suggesting a possible mechanism of action through which this variant may have an effect. These results implicate the calcium channel subunits in antipsychotic treatment response and suggest that increased activation of these channels may be explored to enhance or predict antipsychotic treatment outcome.

Antipsychotics remain the most effective, and wide used option for ameliorating the symptoms of schizophrenia. However, inter-individual differences in treatment outcome are vast and suggest a role for genetic and environmental factors in affording favourable outcomes. A notable epigenetic relationship which has gained considerable traction in recent literature is the way in which the severity of childhood trauma can modify associations seen between genetic variation and antipsychotic treatment response. A potential mechanism of action which may facilitate this relationship is synaptic plasticity. This study investigated the role of variants in matrix metallopeptidase 9 (MMP9), a gene involved in synaptic plasticity, with treatment outcome considering the severity of childhood trauma as an interacting variable. The cohort comprised South African first episode schizophrenia patients treated with a single injectable antipsychotic, flupenthixol decanoate, monitored over 12 months. Relationships between novel and previously described variants, and haplotypes, with antipsychotic treatment response were found to be modified when considering childhood trauma as an interacting variable. This study provides the first evidence for the involvement of polymorphisms within MMP9 and the severity of childhood trauma in antipsychotic treatment response, and warrants further investigation into the role gene-environment interactions may play in the betterment of antipsychotic treatment strategies.

Mental disorders represent a major public health burden worldwide. This is likely to rise in the next decade, with the highest increases predicted to occur in low- and middle-income countries. Current psychotropic medication treatment guidelines focus on uniform approaches to the treatment of heterogeneous disorders and achieve only partial therapeutic success. Developing a global precision medicine approach in psychiatry appears attractive, given the value of this approach in other fields of medicine, such as oncology and infectious diseases. In this horizon scanning analysis, we review the salient opportunities and challenges for precision medicine in psychiatry over the next decade. Variants within numerous genes involved in a range of pathways have been implicated in psychotropic drug response and might ultimately be used to guide choice of pharmacotherapy. Multipronged approaches such as multi-omics (genomics, proteomics, metabolomics) analyses and systems diagnostics together with high-throughput sequencing and genotyping technologies hold promise for identifying precise and targeted treatments in mental disorders. To date, however, the vast majority of pharmacogenomics work has been undertaken in high-income countries on a relatively small proportion of the global population, and many other challenges face the field. Opportunities and challenges for establishing a global roadmap for precision medicine in psychiatry are discussed in this article.

Long-term exposure to efavirenz (EFV) measured in hair samples may predict response to antiretroviral treatment (ART). Polymorphisms in CYP2B6 are known to alter EFV levels. The aim of this study was to assess the relationship between CYP2B6 genotype, EFV levels measured in hair, and virological outcomes on ART in a real-world setting. We measured EFV levels in hair from HIV-positive South African females who had been receiving EFV-based treatment for at least 3 months from the South African Black (SAB) (n = 81) and Cape Mixed Ancestry (CMA) (n = 53) populations. Common genetic variation in CYP2B6 was determined in 15 individuals from each population using bidirectional Sanger sequencing. Prioritized variants (n = 16) were subsequently genotyped in the entire patient cohort (n = 134). The predictive value of EFV levels in hair and selected variants in CYP2B6 on virological treatment outcomes was assessed. Previously described alleles (CYP2B6*2, CYP2B6*5, CYP2B6*6, CYP2B6*17, and CYP2B6*18), as well as two novel alleles (CYP2B6*31 and CYP2B6*32), were detected in this study. Compared to noncarriers, individuals homozygous for CYP2B6*6 had ∼109% increased EFV levels in hair (p = .016) and CYP2B6*18 heterozygotes demonstrated 82% higher EFV hair levels (p = .0006). This study confirmed that alleles affecting CYP2B6 metabolism and subsequent EFV exposure are present at significant frequencies in both the SAB and CMA populations. Furthermore, this study demonstrated that the use of hair samples for testing EFV concentrations may be a useful tool in determining long-term drug exposure in resource-limited countries.

Interindividual and interethnic differences in response to antiretroviral drugs (ARVs) are influenced by genetic variation. The few genomic studies conducted among African-Americans and African ethnic groups do not reflect the extensive genetic diversity within African populations. ARVs are widely used in Africa. Therefore, genomic characterization of African populations is required before genotype-guided dosing becomes possible. The aim of this study was to determine and report on the frequency of genetic variants in genes implicated in metabolism and transport of ARVs in South African populations. The study comprised 48 self-reported South African Colored (SAC) and 296 self-reported Black African (BA) individuals. Allele and genotype frequency distributions for 93 variants contributing to metabolism and transport of ARVs were compared between groups, and other global populations. Fifty-three variants had significant differences in allele and genotype frequencies when comparing SAC and BA groups. Thirteen of these have strong clinical annotations, affecting efavirenz and tenofovir pharmacokinetics. This study provides a summary of the genetic variation within genes implicated in metabolism and transport of ARVs in indigenous South African populations. The observed differences between indigenous population groups, and between these groups and global populations, demonstrate that data generated from specific African populations cannot be used to infer genetic diversity within other populations on the continent. These results highlight the need for comprehensive characterization of genetic variation within indigenous African populations, and the clinical utility of these variants in ARV dosing for global precision medicine. Population pharmacogenetics is a nascent field of global health and warrants further research and education.

Interest in genomics research in African populations is experiencing exponential growth. This enthusiasm stems in part from the recognition that the genomic diversity of African populations is a window of opportunity for innovations in postgenomics medicine, ecology, and evolutionary biology. The recently launched H3Africa initiative, for example, captures the energy and momentum of this interest. This interdisciplinary socio-technical analysis highlights the challenges that have beset previous genomics research activities in Africa, and looking ahead, suggests constructive ways H3Africa and similar large scale science efforts could usefully chart a new era of genomics and life sciences research in Africa that is locally productive and globally competitive. As independent African scholars and social scientists, we propose that any serious global omics science effort, including H3Africa, aiming to build genomics research capacity and capability in Africa, needs to fund the establishment of biobanks and the genomic analyses platforms within Africa. Equally they need to prioritize community engagement and bioinformatics capability an d the training of African scientists on these platform s. Historically , the financial, technological, and skills imbalance between Africa and developed countries has created exploitative frameworks of collaboration where African researchers have become merely facilitators of Western funded and conceived research agendas involving offshore expatriation of samples. Not surprisingly, very little funding was allocated to infrastructure and human capital development in the past. Moving forward, capacity building should materialize throughout the entire knowledge co-production trajectory: idea generation (e.g., brainstorming workshops for innovative hypotheses development by African scientists), data generation (e.g., genome sequencing), an d high-through put data analysis an d contextualization . Additionally, building skills for political science scholarship that questions the unchecked assumptions of the innovation performers be they funders, scientists, and social scientists, would enable collective innovation that is truly sustainable, ethical, and robust.

GPR88, coding for a G protein-coupled orphan receptor that is highly represented in the striatum, is a strong functional candidate gene for neuropsychiatric disorders and is located at 1p22-p21, a chromosomal region that we have previously linked to bipolar disorder (BD) in the Sardinian population. In order to ascertain the relevance of GPR88 as a risk factor for psychiatric diseases, we performed a genetic association analysis between GPR88 and BD in a sample of triads (patient and both parents) recruited in the Sardinian and the Palestinian population as well as between GPR88 and schizophrenia (SZ) in triads from the Xhosa population in South Africa. We found a positive association between GPR88 and BD in the Sardinian and Palestinian triads. Moreover, we found a positive association between GPR88 and SZ in triads from the Xhosa population in South Africa. When these results were corrected for multiple testing, the association between GPR88 and BD was maintained in the Palestinian population. Thus, these results suggest that GPR88 deserves consideration as a candidate gene for psychiatric diseases and requires to be further investigated in other populations.

Pharmacogenomics, personalized medicine and global health are hot topics. They represent enormously active areas of research and development (R&D) and are situated at the epicenter of the genomics innovation and investment agenda, both in developed and resource-limited countries [3]. The theme of “personalization” is taking on global significance in healthcare, not only in the case of drug therapy but also for other interventions such as vaccines and nutrition as well as targeted diagnostics and screening programs for early disease detection and preventive medicine. A fine example of the latter includes testing for deleterious mutations in

1Research Group on Complex Collaboration, Faculty of Management, McGill University 2Centre of Genomics and Policy, Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, QC, Canada 3Data-Enabled Life Sciences Alliance International (DELSA Global), Seattle, WA, USA 4Development Policy and Practice, The Open University, Walton Hall, Milton Keynes, UK 5The ESRC Centre for Social and Economic Research on Innovation in Genomics (Innogen Centre), Milton Keynes, UK 6Columbia Law School – LL.M. Program, New York, NY, USA 7Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences (FM&HS), The University of Auckland, Auckland, New Zealand 8Discipline of Nutrition, FM&HS, The University of Auckland, Auckland, New Zealand 9Nutrigenomics New Zealand, New Zealand 10Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece 11Clinical Pharmacology Unit, Academic General Hospital of Alexandroupolis, Alexandroupolis, Greece 12European Society of Pharmacogenomics and Theranostics 13L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada 14Faculty of Private Law, University of Cape Town, Cape Town, South Africa 15Department of Genetics, Stellenbosch University, Stellenbosch, South Africa 16Wadhwani Research Center for Biosciences and Bioengineering, Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, India

BACKGROUND Although antipsychotics are integral to the treatment of schizophrenia, drug efficacy varies between patients. Although it has been shown that antipsychotic treatment response outcomes are heritable, our understanding of the genetic factors that are involved remains incomplete. Therefore, this study aims to use an unbiased scan of the genome to identify the genetic variants contributing toward antipsychotic treatment response outcomes. MATERIALS AND METHODS This study utilized whole-exome sequencing of patients on extreme ends of the treatment response spectrum (n=11) in combination with results from previous antipsychotic studies to design a panel of variants that were genotyped in two well-characterized first-episode schizophrenia cohorts (n=103 and 87). Association analyses were carried out to determine whether these variants were significantly associated with antipsychotic treatment response outcomes. RESULTS Association analyses in the discovery cohort identified two nonsynonymous variants that were significantly associated with antipsychotic treatment response outcomes (P

In order to optimize treatment outcome among antiretroviral therapy users, there is a strong imperative to engage in continued monitoring and maintenance of therapeutic drug levels in patients. The aim of this study was to document the perspectives, beliefs, and concerns of South African antiretroviral therapy users providing hair specimens to determine antiretroviral drug levels. Twenty-one women living with HIV were recruited from a community health center in the Western Cape. Interviews were recorded and transcribed, and analyzed using Atlas.ti version 6. Although participants identified several cultural beliefs influencing their decision to provide hair specimens for drug level measurement, nearly all agreed that they would be willing to do so if provided with enough information by the researcher.

Africa is the cradle of mankind. African science and knowledge-based innovation are central to a deep understanding of pathophysiology, prevention and treatment of human diseases, discovery and development of novel diagnostics, as well as ecosystem health (Roetz and Warnich, 2013; Rotimi, 2012). The ‘‘OMICS IN AFRICA’’ special issue in July is a precious contribution to 21 century life sciences, medicine, and global health. The issue presents a timely sample of cutting edge research from Africa, and brings about diverse perspectives emerging from lab-to-society that will collectively inform how best to design and sustain a robust innovation ecosystem in Africa.

Metabolic syndrome (MetS) is a cluster of factors that increases the risk of cardiovascular disease (CVD), one of the leading causes of mortality in patients with schizophrenia. Incidence rates of MetS are significantly higher in patients with schizophrenia compared to the general population. Several factors contribute to this high comorbidity. This systematic review focuses on genetic factors and interrogates data from association studies of genes implicated in the development of MetS in patients with schizophrenia. We aimed to identify variants that potentially contribute to the high comorbidity between these disorders. PubMed, Web of Science and Scopus databases were accessed and a systematic review of published studies was conducted. Several genes showed strong evidence for an association with MetS in patients with schizophrenia, including the fat mass and obesity associated gene (FTO), leptin and leptin receptor genes (LEP, LEPR), methylenetetrahydrofolate reductase (MTHFR) gene and the serotonin receptor 2C gene (HTR2C). Genetic association studies in complex disorders are convoluted by the multifactorial nature of these disorders, further complicating investigations of comorbidity. Recommendations for future studies include assessment of larger samples, inclusion of healthy controls, longitudinal rather than cross-sectional study designs, detailed capturing of data on confounding variables for both disorders and verification of significant findings in other populations. In future, big genomic datasets may allow for the calculation of polygenic risk scores in risk prediction of MetS in patients with schizophrenia. This could ultimately facilitate early, precise, and patient-specific pharmacological and non-pharmacological interventions to minimise CVD associated morbidity and mortality.

The conventional drug development paradigm can test new drug candidates only in a limited number of patients and healthy volunteers, typically in the order of a few thousand at most. While the common adverse drug reactions (ADRs) are discerned prior to clinical use, less common or rare ADRs and population-wide efficacy of new drugs are often delineated in greater granularity after regulatory approval in clinical practice. In some cases, serious ADRs may be discovered as long as 36 years after a drug receives regulatory approval (Ladewski et al., 2003). Surveillance of drug safety and efficacy after regulatory approval, pharmacovigilance, is therefore a centerpiece concept in clinical pharmacology and population health. Since the 1970s, governments around the world have established institutions for regulatory science and pharmacovigilance, although they remain cursory in many parts of the developing world. Early signal detection and mechanistic evaluation of ADRs and drug efficacy, not to mention extrapolation of pharmacovigilance data from populationto-population (i.e., population bridging), are areas of active research in rational therapeutics and postgenomics medicine. Health technology assessment (HTA), for example, has led to development of smart decision tools and foresight methods that inform postmarketing surveillance, and are relevant for other health products such as vaccines and nutritional supplements as well. Put in other words, pharmacovigilance aims to understand the epidemiology and mechanisms of vast heterogeneity in drug-related outcomes, be they ADRs or therapeutic outcomes, at an individual and population scale. Pharmacogenomics, another field of 21 century integrative biology, aims to explain the genomics basis individual differences in drug safety and efficacy. The new term pharmacogenovigilance, coined first by Sxardas x in 2010, is defined as ‘‘pharmacovigilance activities informed and guided by accompanying pharmacogenomics analyses.’’ (Sxardas x, 2010). Because both pharmacovigilance and pharmacogenomics share the objective of explaining person-to-person and between-population heterogeneity in drug pharmacokinetics and pharmacodynamics, pharmacogenovigilance buttresses the current efforts for rational and mechanistically informed monitoring of drugs. The integration of pharmacovigilance and pharmacogenomics activities under the rubric of the new field of pharmacogenovigilance offers much conceptual and practical advances, and are described in detail elsewhere (Sxardas x, 2010). For our purposes in this editorial, we wish to emphasize, however, that pharmacogenovigilance by virtue of its incorporation of pharmacogenomics biomarkers, is more mechanistic in its approach to surveillance than traditional pharmacovigilance. Such mechanistic orientation enables

Biological processes are fundamentally driven by complex interactions between biomolecules. Integrated high-throughput omics studies enable multifaceted views of cells, organisms, or their communities. With the advent of new post-genomics technologies, omics studies are becoming increasingly prevalent; yet the full impact of these studies can only be realized through data harmonization, sharing, meta-analysis, and integrated research. These essential steps require consistent generation, capture, and distribution of metadata. To ensure transparency, facilitate data harmonization, and maximize reproducibility and usability of life sciences studies, we propose a simple common omics metadata checklist. The proposed checklist is built on the rich ontologies and standards already in use by the life sciences community. The checklist will serve as a common denominator to guide experimental design, capture important parameters, and be used as a standard format for stand-alone data publications. The omics metadata checklist and data publications will create efficient linkages between omics data and knowledge-based life sciences innovation and, importantly, allow for appropriate attribution to data generators and infrastructure science builders in the post-genomics era. We ask that the life sciences community test the proposed omics metadata checklist and data publications and provide feedback for their use and improvement.

Aim: Many antipsychotic pharmacogenetics studies have been performed examining candidate genes or known variation; however, our understanding of the genetic factors involved in antipsychotic pharmacogenetic traits remains limited. Materials & methods: A well-characterized cohort of first-episode schizophrenia (FES) patients was used to identify a subset of nonresponders and responders to antipsychotic treatment for exome sequencing (n = 11). The variation observed in the responders and nonresponders was subsequently compared and a prioritization strategy was employed to identify variants for genotyping in the entire FES cohort (n = 103) as well as an additional Xhosa schizophrenia cohort (n = 222). Results: Examination of coding variation revealed a potential role for rare loss-of-function variants in treatment response outcomes. One variant, rs11368509, was found to be weakly associated with better treatment outcomes in the FES cohort (p = 0.057) and the Xhosa schizophrenia cohort (p = 0.016). In addition, the majority of the loss-of-function variation that was considered likely to be involved in antipsychotic treatment response was either novel or rare in Asian and European populations. Conclusion: This pilot study has highlighted the importance of exome sequencing for antipsychotic pharmacogenomics studies, particularly in African individuals. Furthermore, the results emphasize once again the complexity of antipsychotic pharmacogenomics and the need for future research. Original submitted 8 July 2013; Revision submitted 24 October 2013

This article announces the recipient of the 2014 inaugural Werner Kalow Responsible Innovation Prize in Global Omics and Personalized Medicine by the Pacific Rim Association for Clinical Pharmacogenetics (PRACP): Bernard Lerer, professor of psychiatry and director of the Biological Psychiatry Laboratory, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. The Werner Kalow Responsible Innovation Prize is given to an exceptional interdisciplinary scholar who has made highly innovative and enduring contributions to global omics science and personalized medicine, with both vertical and horizontal (transdisciplinary) impacts. The prize is established in memory of a beloved colleague, mentor, and friend, the late Professor Werner Kalow, who cultivated the idea and practice of pharmacogenetics in modern therapeutics commencing in the 1950s. PRACP, the prize's sponsor, is one of the longest standing learned societies in the Asia-Pacific region, and was founded by Kalow and colleagues more than two decades ago in the then-emerging field of pharmacogenetics. In announcing this inaugural prize and its winner, we seek to highlight the works of prize winner, Professor Lerer. Additionally, we contextualize the significance of the prize by recalling the life and works of Professor Kalow and providing a brief socio-technical history of the rise of pharmacogenetics and personalized medicine as a veritable form of 21(st) century scientific practice. The article also fills a void in previous social science analyses of pharmacogenetics, by bringing to the fore the works of Kalow from 1995 to 2008, when he presciently noted the rise of yet another field of postgenomics inquiry--pharmacoepigenetics--that railed against genetic determinism and underscored the temporal and spatial plasticity of genetic components of drug response, with invention of the repeated drug administration (RDA) method that estimates the dynamic heritabilities of drug response. The prize goes a long way to cultivate transgenerational capacity and broader cognizance of the concept and practice of responsible innovation as an important criterion of 21(st) century omics science and personalized medicine. A new call is presently in place for the 2016 PRACP Werner Kalow prize. Nominations can be made in support of an exceptional individual interdisciplinary scholar, or alternatively, an entire research team, from any region in the world with a record of highly innovative contributions to global omics science and/or personalized medicine, in the spirit of responsible innovation. The application process is straightforward, requiring a signed, 1500-word nomination letter (by the applicant or sponsor) submitted not later than May 31, 2015.

Because of the unmet needs of current pharmacotherapy for schizophrenia, antipsychotic pharmacogenetic research is of utmost importance. However, to date, few clinically applicable antipsychotic pharmacogenomic alleles have been identified. Nonetheless, next-generation sequencing technologies are expected to aid in the identification of clinically significant variants for this complex phenotype. The aim of this study was therefore to critically examine the ability of next-generation sequencing technologies to reliably detect variation present in pharmacogenes.Candidate antipsychotic pharmacogenes and very important pharmacogenes were identified from the literature and the Pharmacogenomics Knowledgebase. Thereafter, the percentage sequence similarity observed between these genes and their corresponding pseudogenes and paralogues, as well as the percentage low-complexity sequence and GC content of each gene, was calculated. These sequence attributes were subsequently compared with the 'inaccessible' regions of these genes as described by the 1000 Genomes Project.It was found that the percentage 'inaccessible genome' correlated well with GC content (P=9.96×10), low-complexity sequence (P=0.0002) and the presence of pseudogenes/paralogues (P=8.02×10). In addition, it was found that many of the pharmacogenes were not ideally suited to next-generation sequencing because of these genomic complexities. These included the CYP and HLA genes, both of which are of importance to many fields of pharmacogenetics.Current short read sequencing technologies are unable to comprehensively capture the variation in all pharmacogenes. Therefore, until high-throughput sequencing technologies advance further, it may be necessary to combine next-generation sequencing with other genotyping strategies.

Vural Ozdemir1,*, Erik Fisher2, Edward S. Dove1, Hilary Burton3, Galen E. B. Wright4, Mario Masellis5,*, and Louise Warnich4,* 1Centre of Genomics and Policy, Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, QC, Canada 2School of Politics and Global Studies, Consortium for Science, Policy & Outcomes, Center for Nanotechnology in Society, College of Liberal Arts and Sciences, Arizona State University, Tempe, AZ, USA 3Foundation for Genomics and Population Health, 2 Worts Causeway, Cambridge, UK 4Department of Genetics, Stellenbosch University, Stellenbosch, South Africa 5L.C. Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Department of Medicine (Neurology), Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada

Chromosome 22q11 aberrations substantially increase the risk for developing schizophrenia. Although micro-deletions in this region have been extensively investigated in different populations across the world, little is known of their prevalence in African subjects with schizophrenia. We screened 110 African Xhosa-speaking participants with schizophrenia for the presence of micro-deletions. As further verification for the presence or absence of 22q11 microdeletions, we screened 238 Xhosa schizophrenia patients and 240 healthy Xhosa individuals from a larger schizophrenia candidate 22q11 gene study using molecular analyses. Data from molecular and cytogenetic analyses confirmed the absence of 22q11 microdeletions in the Xhosa schizophrenia samples. Although the absence of chromosome 22q11 micro-deletions in this group of patients does not exclude the possibility that it may occur in Xhosa schizophrenia patients, we concluded an extremely low prevalence. Our findings suggest that unique susceptibility loci may be present in this group.

Psychiatric disorders place a considerable healthcare burden on South African society. Incorporating genetic technologies into future treatment plans offers a potential mechanism to reduce this burden. This review focuses on psychiatric genetic research that has been performed in South African populations with regards to obsessive-compulsive disorder, schizophrenia and bipolar disorder. Preliminary findings from these studies suggest that data obtained in developed countries cannot necessarily be extrapolated to South African population groups. Psychiatric genetic studies in South Africa seem to involve relatively low-cost methodologies and only a limited number of large national collaborative studies. Future research in South Africa should therefore aim to incorporate highthroughput technologies into large scale psychiatric studies through the development of collaborations. On a global level, the vast majority of psychiatric genetic studies have been performed in non-African populations. South Africa, as the leading contributor to scientific research in Africa, may provide a foundation for addressing this disparity and strengthening psychiatric genetic research on the continent. Although the elucidation of the genetic architecture of psychiatric disorders has proved challenging, examining the unique genetic profiles found in South African populations could provide valuable insight into the genetics of psychiatric disorders.Keywords: Bipolar disorder; Obsessive-compulsive disorder; Pharmacogenetics; Psychiatric genetics; Schizophrenia; South African populations

Anticipatory ethics, Data-Enabled Life Sciences Alliance, DELSA, genomics without borders, global ethics and international development in pharmacogenomics, Human Variome Project, RaDiCAL, Rare Disease Consortium for Autosomal Loci. “Where the common disease communities bring opportunities of scale, the heritable disease community brings insights from detail and experience. Both are concerned with personalized medicine and should work together.”

The purpose of this study was to assess the likelihood that variation in the promoter region of the solute carrier family 11 member 1 gene (SLC11A1) contributes to inflammatory bowel disease (IBD) susceptibility in the South African population. The study cohort included 102 IBD patients, 47 with Crohn's disease (CD) and 55 with ulcerative colitis, and 192 population-matched controls. Mutation analysis revealed two novel alleles for the 5′-(GT)n repeat polymorphism, t(gt)5ac(gt)5ac(gt)6ggcaga(g)6 (allele 8) and t(gt)5ac(gt)5ac(gt)8ggcaga(g)6 (allele 9), and one previously documented point mutation −237C→T. A significantly decreased frequency of the −237C→T promoter polymorphism was observed in the patient group with IBD (p

Mutations in the UROD gene are demonstrable in approximately only one quarter of all familial porphyria cutanea tarda (PCT) cases with a typical 50% decrease in the catalytic activity of hepatic UROD.1 In the remaining 75% of cases, there is no underlying mutation in the UROD gene, and the disease results from an acquired inhibition of hepatic UROD, referred to as sporadic PCT. Of importance is a near-universal association between PCT and raised hepatic iron concentrations. Most patients with PCT will have evidence of direct or indirect iron overload, and PCT appears not to develop in the absence of adequate iron stores.1 ,2 Iron alone is insufficient for the precipitation of PCT. It is, however, clear that a complex gene-chemical-environmental interaction is pivotal to the process.2 Our study focused on the regulatory (promoter) regions of four genes that play a significant role in iron homeostasis: ceruloplasmin ( CP ), cytochrome b reductase 1 ( CYBRD1 ), hepcidin antimicrobial peptide ( HAMP ) and solute carrier family 40 member A1 ( SLC40A1 ). ### Study cohort Blood samples were collected from 74 unrelated South African patients (39 male, 35 female) who presented with clinically expressed PCT. Ethnically, the study group included 15 indigenous African patients, eight males (mean age of onset: 49.88±21 years), seven females …