Maternal stress has been linked to low birth weight in newborns. One potential pathway involves epigenetic changes at candidate genes that may mediate the effects of prenatal maternal stress on birth weight. This relationship has been documented in stress-related genes, such as NR3C1 . There is less literature exploring the effect of stress on growth-related genes. IGF1 and IGF2 have been implicated in fetal growth and development, though via different mechanisms as IGF2 is under imprinting control. In this study, we tested for associations between prenatal stress, methylation of IGF1 and IGF2 , and birth weight. A total of 24 mother–newborn dyads in the Democratic Republic of Congo were enrolled. Ethnographic interviews were conducted with mothers at delivery to gather culturally relevant war-related and chronic stressors. DNA methylation data were generated from maternal venous, cord blood and placental tissue samples. Multivariate regressions were used to test for associations between stress measures, DNA methylation and birth weight in each of the three tissue types. We found an association between IGF2 methylation in maternal blood and birth weight. Previous literature on the relationship between IGF2 methylation and birth weight has focused on methylation at known differentially methylated regions in cord blood or placental samples. Our findings indicate there may be links between the maternal epigenome and low birth weight that rely on mechanisms outside known imprinting pathways. It thus may be important to consider the effect of maternal exposures and epigenetic profiles on birth weight even in the setting of maternally imprinted genes such as IGF2 .
The effects of stress on ill health have become evident in recent years. Under acute stress situations, a cascade of physiological events helps the body mount an appropriate adaptive response. However, under chronic stress situations, this physiological response may lead to wear and tear on the body that accelerates the decline in physiological functioning and increases the risk of chronic conditions. Recent evidence for social stress experienced during childhood suggests serious consequences many years later, even later life. Telomere length, a marker of cell aging, may provide a link between chronic social stress and age-associated physical and mental decline and risk of chronic conditions. This study examines whether chronic social stress is associated with telomere length throughout the life course. We will perform a systematic review of the literature on the relationship between chronic social stress, for example, due to violence, extreme poverty, or caregiving of people with disabling conditions (exposure), and telomere length (outcome) by searching electronic databases in MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and gray literature from their start date onwards. We will limit the search to studies performed on human populations. Two reviewers will conduct standardized screening, eligibility assessment, data abstraction, and scientific quality assessment. All study designs investigating the association between chronic social stress and telomere length in healthy or diseased adults and children will be eligible for inclusion in the review. We will extract individual demographic and socioeconomic characteristics, research setting, method of measuring telomere length, reported outcome, and determinants of interest. Studies will also be stratified by 1) age into 3 groups: childhood (0 to 18 years), adulthood (19 to 64 years) and late life (65+); 2) cell type; 3) study design; and 4) telomere length assessment method. Where feasible, study results will be combined through meta-analyses to obtain a pooled measure of associations. Results will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. This systematic review will provide knowledge on the existing evidence for chronic social stress and its association with telomere lengths throughout the life course.
Despite recent large-scale investments, malaria remains a major public health concern. Few studies have examined congenital malaria, defined as the presence of malaria parasitemia within the first 7 days of life, in endemic areas. This study aimed to determine the prevalence, to describe the clinical presentation, and to examine factors associated with congenital malaria in newborns aged up to 7 days attending Tororo General Hospital in Uganda. A total of 261 mother/baby pairs were recruited in this cross-sectional study. Giemsa-stained thick blood smears for malaria parasites and rapid malaria diagnostic tests were performed on capillary blood samples from all newborns and mothers, as well as on placental and cord samples from newborns delivered in the hospital. The prevalence of congenital malaria in the newborns was 16/261 (6.1%). No single clinical feature was associated with congenital malaria. However, there were associations between congenital malaria and maternal parasitemia (P < 0.001), gravidity of one (P = 0.03), maternal age < 19 years (P = 0.01), cord blood parasitemia (P = 0.01), and placental malaria (P = 0.02). In conclusion, congenital malaria is not rare in Uganda and there are no obvious clinical features associated with it in the newborn. Based on these findings, we recommend strengthening malaria prevention during pregnancy to reduce the occurrence of congenital malaria in newborns.
African Americans are 40% more likely to be afflicted with hypertension than are non-Hispanic, white Americans, resulting in a 30% higher instance of mortality due to cardiovascular disease. There is debate about the relative contributions of genetic and sociocultural risk factors to the racial disparity in hypertension. We assayed three Alu insertion polymorphisms located in the ACE (angiotensin 1 converting enzyme), PLAT (plasminogen activator, tissue), and WNK1 (lysine deficient protein kinase 1) genes. We also estimated West African genetic ancestry and developed novel measures of perceived discrimination to create a biocultural model of blood pressure among African American adults in Tallahassee, Florida (n = 158). When tested separately, the ACE Alu noninsertion allele was significantly associated with higher systolic and diastolic blood pressure. In multiple regression analyses, West African genetic ancestry was not associated with blood pressure and reduced the strength of all blood pressure models tested. A gene × environment interaction was identified between the ACE Alu genotype and a new measure of unfair treatment that includes experiences by individuals close to the study participant. Inclusion of the WNK1 Alu genotype further improved this model of blood pressure variation. Our results suggest an association of the ACE and WNK1 genotypes with blood pressure that is consistent with their proposed gene functions. Measures of perceived unfair treatment of others show a threshold effect, with increased blood pressure occurring at higher values. The interaction between the ACE genotype and unfair treatment highlights the benefits of including both genetic and cultural data to investigate complex disease.
Background: Upper gastrointestinal bleeding (UGIB) is a common cause of admission and death in the gastroenterology service. The prevalence, risk factors and the case fatality rate of UGIB may differ by settings.
Objectives: Our objective was to determine the prevalence of symptoms and the case fatality rate of UGIB among patients at the gastroenterology service of Mulago Hospital in Kampala, Uganda and to describe the clinical and laboratory risk fac- tors associated with the survival of these patients.
Methods: In a cross-sectional study performed between September 2013 and April 2014, patients were screened for UGIB symptoms. Data was collected on socio-demographic characteristics, clinical presentation and patient’s outcome within one week of admission. Bivariate, multivariate, and survival analysis were performed to identify variables that were significantly associated with mortality.
Results: Out of 1085 patients screened, we identified the prevalence of UGIB symptoms in 220 patients (20.3%). Among these, 150 met the inclusion criteria for our study. The majority were males (70.7%) and 40 years of age or less (60%). The most prevalent clinical diagnosis were gastritis (39.3%), esophageal varices (17.3%) and peptic ulcer disease (PUD) (16%). Among patients who underwent endoscopy, esophageal varices (42.2%), PUD (26.3%) and gastritis (15.8%) were the lead- ing causes of bleeding. The overall case fatality rate was 16.7% (25/150). Uremia remained associated with mortality after controlling for confounders. Survival was significantly reduced for males as well as for patients with uremia and malignancy.
Conclusion: the prevalence of symptoms and the case fatality rate of UGIB among patients admitted to the gastroenter- ology ward in Mulago hospital were higher than in developed countries and similar to other resource-limited setting. The majority of patients were young men and presented with both hematemesis and melena. The most common causes of UGIB were esophageal varices, gastritis and PUD. Survival analysis indicate that male gender, uremia, and malignancy are associated with reduced survival.
Keyword: Upper gastrointestinal bleeding; gastroenterology; survival; Uganda; Africa.
Sequencing of the human genome and decades of genetic association and linkage studies have dramatically improved our understanding of the etiology of many diseases. However, the multiple causes of complex diseases are still not well understood, in part because genetic and sociocultural risk factors are not typically investigated concurrently. Hypertension is a leading risk factor for cardiovascular disease and afflicts more African Americans than any other racially defined group in the US. Few genetic loci for hypertension have been replicated across populations, which may reflect population-specific differences in genetic variants and/or inattention to relevant sociocultural factors. Discrimination is a salient sociocultural risk factor for poor health and has been associated with hypertension. Here we use a biocultural approach to study blood pressure (BP) variation in African Americans living in Tallahassee, Florida by genotyping over 30,000 single nucleotide polymorphisms (SNPs) and capturing experiences of discrimination using novel measures of unfair treatment of self and others (n = 157). We perform a joint admixture and genetic association analysis for BP that prioritizes regions of the genome with African ancestry. We only report significant SNPs that were confirmed through our simulation analyses, which were performed to determine the false positive rate. We identify eight significant SNPs in five genes that were previously associated with cardiovascular diseases. When we include measures of unfair treatment and test for interactions between SNPs and unfair treatment, we identify a new class of genes involved in multiple phenotypes including psychosocial distress and mood disorders. Our results suggest that inclusion of culturally relevant stress measures, like unfair treatment in African Americans, may reveal new genes and biological pathways relevant to the etiology of hypertension, and may also improve our understanding of the complexity of gene-environment interactions that underlie complex diseases.
