Epigenome-wide association study of plasma lipids in West Africans: the RODAM study

BACKGROUND: DNA-methylation has been associated with plasma lipid concentration in populations of diverse ethnic backgrounds, but epigenome-wide association studies (EWAS) in West-Africans are lacking. The aim of this study was to identify DNA-methylation loci associated with plasma lipids in Ghanaians. METHODS: We conducted an EWAS using Illumina 450k DNA-methylation array profiles of extracted DNA from 663 Ghanaian participants. Differentially methylated positions (DMPs) were examined for association with plasma total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, and triglycerides concentrations using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, and technical covariates. Findings were replicated in independent cohorts of different ethnicities. FINDINGS: We identified one significantly associated DMP with triglycerides (cg19693031 annotated to TXNIP, regression coefficient beta -0.26, false discovery rate adjusted p-value 0.001), which replicated in-silico in South African Batswana, African American, and European populations. From the top five DMPs with the lowest nominal p-values, two additional DMPs for triglycerides (CPT1A, ABCG1), two DMPs for LDL-cholesterol (EPSTI1, cg13781819), and one for TC (TXNIP) replicated. With the exception of EPSTI1, these loci are involved in lipid transport/metabolism or are known GWAS-associated loci. The top 5 DMPs per lipid trait explained 9.5% in the variance of TC, 8.3% in LDL-cholesterol, 6.1% in HDL-cholesterol, and 11.0% in triglycerides. INTERPRETATION: The top DMPs identified in this study are in loci that play a role in lipid metabolism across populations, including West-Africans. Future studies including larger sample size, longitudinal study design and translational research is needed to increase our understanding on the epigenetic regulation of lipid metabolism among West-African populations. FUNDING: European Commission under the Framework Programme (grant number: 278901)

Total Serum Magnesium Levels and Calcium-To-Magnesium Ratio in Sickle Cell Disease

Background and Objectives: Imbalance of calcium/magnesium ratio could lead to clinical complications in sickle cell disease (SCD). Low levels of magnesium have been associated with sickling, increased polymerization and vaso-occlusion (VOC) in sickle cell due to cell dehydration. The K-Cl cotransport plays a very important role in sickle cell dehydration and is inhibited by significantly increasing levels of magnesium. The study evaluated total serum magnesium levels and computed calcium/magnesium ratio in SCD patients and “healthy” controls. Materials and Methods: The study was a case-control cross-sectional one, involving 120 SCD patients (79 Haemoglobin SS (HbSS)and 41 Haemoglobin SC (HbSC)) at the steady state and 48 “healthy” controls. Sera were prepared from whole blood samples (n = 168) and total magnesium and calcium measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd., Melbourne, VIC, Australia). Calcium/magnesium ratios were calculated in patients and the controls. Results: The prevalence of hypomagnesemia and hypocalcaemia among the SCD patients was observed to be 39.17% and 52.50% respectively, higher than the controls (4.17% and 22.92%, for hypomagnesemia and hypocalcaemia, respectively). Level of magnesium was significantly lower in the SCD patients compared to their healthy counterparts (p = 0.002). The magnesium level was further reduced in the HbSS patients but not significantly different from the HbSC patients (p = 0.584). calcium/magnesium ratio was significantly higher in the SCD patients (p = 0.031). Although calcium/magnesium ratio was higher in the HbSC patients compared to those with the HbSS genotype, the difference was not significant (p = 0.101). Conclusion: The study shows that magnesium homeostasis are altered in SCD patients, and their levels are lower in HbSS patients. Although calcium/magnesium ratio is significantly higher in SCD patients compared with controls, there is no significant difference between patients with HbSS and HbSC genotypes. Magnesium supplementation may be required in sickle cell patients

Total Serum Magnesium Levels and Calcium-To-Magnesium Ratio in Sickle Cell Disease

Background and objectives: Imbalance of calcium/magnesium ratio could lead to clinical complications in sickle cell disease (SCD). Low levels of magnesium have been associated with sickling, increased polymerization and vaso-occlusion (VOC) in sickle cell due to cell dehydration. The K-Cl cotransport plays a very important role in sickle cell dehydration and is inhibited by significantly increasing levels of magnesium. The study evaluated total serum magnesium levels and computed calcium/magnesium ratio in SCD patients and "healthy" controls. Materials and methods: The study was a case-control cross-sectional one, involving 120 SCD patients (79 Haemoglobin SS (HbSS)and 41 Haemoglobin SC (HbSC)) at the steady state and 48 "healthy" controls. Sera were prepared from whole blood samples (n = 168) and total magnesium and calcium measured using a Flame Atomic Absorption Spectrometer (Variant 240FS manufactured by VARIAN Australia Pty Ltd., Melbourne, VIC, Australia). Calcium/magnesium ratios were calculated in patients and the controls. Results: The prevalence of hypomagnesemia and hypocalcaemia among the SCD patients was observed to be 39.17% and 52.50% respectively, higher than the controls (4.17% and 22.92%, for hypomagnesemia and hypocalcaemia, respectively). Level of magnesium was significantly lower in the SCD patients compared to their healthy counterparts (p = 0.002). The magnesium level was further reduced in the HbSS patients but not significantly different from the HbSC patients (p = 0.584). calcium/magnesium ratio was significantly higher in the SCD patients (p = 0.031). Although calcium/magnesium ratio was higher in the HbSC patients compared to those with the HbSS genotype, the difference was not significant (p = 0.101). Conclusion: The study shows that magnesium homeostasis are altered in SCD patients, and their levels are lower in HbSS patients. Although calcium/magnesium ratio is significantly higher in SCD patients compared with controls, there is no significant difference between patients with HbSS and HbSC genotypes. Magnesium supplementation may be required in sickle cell patients

Association between C reactive protein and microvascular and macrovascular dysfunction in sub-Saharan Africans with and without diabetes: the RODAM study

Introduction Although inflammation assessed by elevated C reactive protein (CRP) concentration is known to be associated with risk of cardiovascular disease, its association with microvascular and macrovascular dysfunction in diabetes and non-diabetes remains unclear. We examined the association between CRP and diabetes and associated microvascular and macrovascular dysfunction in sub-Saharan Africans with and without diabetes.Research design and methods Cross-sectional analyses of baseline data from the multicenter RODAM study (Research on Obesity and Diabetes among African Migrants) including 5248 Ghanaians (583 with diabetes, 4665 without diabetes) aged 25–70 years were done. Logistic regression analyses were used to examine the associations between CRP Z-scores and diabetes and microvascular (nephropathy) and macrovascular (peripheral artery disease (PAD)) dysfunction, with adjustments for age, sex, site of residence, smoking, body mass index, systolic blood pressure, and low-density lipoprotein cholesterol.Results In the fully adjusted models, higher CRP concentration was significantly associated with diabetes (adjusted OR 1.13; 95% CI 1.05 to 1.21, p=0.002). In participants with diabetes, higher CRP concentration was associated with PAD (1.19; 1.03 to 1.41, p=0.046) but not nephropathy (1.13; 0.97 to 1.31, p=0.120). Among participants without diabetes, higher CRP concentration was associated with higher odds of PAD (1.10; 1.01 to 1.21, p=0.029) and nephropathy (1.12; 1.04 to 1.22, p=0.004).Conclusions In this study, higher CRP concentration was associated with higher odds of diabetes in sub-Saharan Africans. Also, higher CRP concentration was associated with higher odds of nephropathy and PAD in non-diabetes and higher odds of PAD in diabetes. CRP may be an important marker for assessment of risk of diabetes and risk for PAD and nephropathy in sub-Saharan Africans with and without diabetes

Associations of Serum Uric Acid Levels with Macrovascular and Renal Microvascular Dysfunction among Individuals from Sub-Saharan Africa

Importance: Serum uric acid (SUA) level is associated with vascular dysfunction in Eurasian populations, but little is known about this association in individuals from sub-Saharan Africa, who have a high prevalence of both relatively high SUA levels and vascular dysfunction. Objectives: To assess the associations of SUA levels with macrovascular and kidney microvascular dysfunction in individuals of sub-Saharan African ancestry and evaluate potential factors that could mediate these associations. Design, Setting, and Participants: Cross-sectional analyses of baseline data from the multicenter Research on Obesity and Diabetes Among African Migrants study, conducted from 2012 to 2015, were performed from January to March 2021. The population included Ghanaian individuals living in Ghana and Europe. Exposure: Abnormal SUA levels. Main Outcomes and Measures: Logistic regression was used to examine the associations of SUA level quartiles with microvascular (albuminuria) and macrovascular (peripheral artery disease and coronary artery disease) dysfunction, with adjustments for age, sex, estimated glomerular filtration rate, site of residence, socioeconomic status, alcohol, smoking, diabetes, hypertension, waist-hip ratio, and total cholesterol level. Mediation analysis was performed to assess whether the association was via elevated blood pressure, hemoglobin A1c, and high-sensitivity C-reactive protein levels or via weight-hip ratio. The research questions were formulated after data collection. Results: A total of 4919 Ghanaian individuals (3047 [61.9%] women) aged 25-75 years (mean [SD], 46.26 [11.08] years) were included. There was a significant positive association between SUA quartiles and albuminuria, but not coronary artery disease or peripheral artery disease, after adjustment for covariates. After full adjustment, individuals in the fourth SUA quartile had higher odds of albuminuria (adjusted odds ratio [aOR], 1.54; 95% CI, 1.07-2.21), but not peripheral artery disease (aOR, 1.35; 95% CI, 0.87-2.08) or coronary artery disease (aOR, 1.09; 95% CI, 0.77-1.55), compared with individuals in the first quartile. After full adjustment, systolic and diastolic blood pressure significantly mediated the association between SUA concentrations and albuminuria, accounting for 19.4% of the total association for systolic and 17.2% for diastolic blood pressure; hemoglobin A1c, high-sensitivity C-reactive protein, and waist-hip ratio did not mediate this association. Conclusions and Relevance: In this cross-sectional study among a sub-Saharan African population, elevated SUA levels were significantly associated with kidney microvascular dysfunction and mediated partly through elevated blood pressure. These findings suggest that individuals from sub-Saharan Africa with elevated SUA levels may benefit from periodic screening for kidney microvascular dysfunction to aid early detection or treatment

A Cross-Sectional Study of Ocular Changes in Children and Adolescents with Diabetes Mellitus in Selected Health Facilities in Ghana

Background: The main objective of the study was to determine the prevalence of diabetic retinopathy (DR), other diabetes-related ocular changes (e.g., cataracts, corneal ulceration), and non-diabetic ocular disease in Ghanaian children and adolescents. The second objective was to evaluate the relationship between these conditions and age at diagnosis, current age, diabetes mellitus (DM) duration, and participant’s sex. Methods: A cross-sectional study, undertaken by a multidisciplinary team, included a cohort of children and adolescents (4–19 years) with DM recruited from selected health facilities in Ghana, from March 2016 to September 2019, after written informed consent or assent. The cohort will be followed up for 3 years to determine the natural course of the ocular changes, reported later. Participants were examined for all microvascular and macrovascular complications, non-diabetic ocular disease, anthropometric measurements, laboratory characteristics and quality of life issues. Full ocular examination was also undertaken. Statistical Package for Social Sciences (SPSS Version 25.0) was used for the data analysis. Continuous and categorical variables were presented as mean and standard deviation (SD), median (interquartile range) and as percentages (%), respectively. T-test and Mann–Whitney U test were used in establishing associations. Results: A total of 58 participants were recruited. DR was detected in only 1 out of 58 (1.7%) participants at baseline. Cataracts were the most common ocular finding, detected in 42 (72%) at baseline. Other anterior segment changes observed included blepharitis 46 (79.3%) and tear film instability 38 (65.5%). There was a significant positive association between duration of the DM and the risk of cataract (p = 0.027). Participants’ age at diagnosis was significantly associated with the presence of prominent corneal nerves (p = 0.004). Conclusions: DR was uncommon in this cohort of young persons with DM in Ghana. Cataracts, blepharitis and refractive errors were ocular changes commonly observed. All young persons with diabetes should undergo regular eye examination in all clinics where follow-up care is provided