scholarly journals A KIR B centromeric region present in Africans but not Europeans protects pregnant women from pre-eclampsia

2015 ◽  
Vol 112 (3) ◽  
pp. 845-850 ◽  
Author(s):  
Annettee Nakimuli ◽  
Olympe Chazara ◽  
Susan E. Hiby ◽  
Lydia Farrell ◽  
Stephen Tukwasibwe ◽  
...  
Keyword(s):  
Risk Factor ◽  
Maternal Mortality ◽  
Odds Ratio ◽  
Centromeric Region ◽  
Killer Cell ◽  
Mulago Hospital ◽  
Genetic Studies ◽  
African Populations ◽  
Sub Saharan ◽  
European Populations

In sub-Saharan Africans, maternal mortality is unacceptably high, with >400 deaths per 100,000 births compared with <10 deaths per 100,000 births in Europeans. One-third of the deaths are caused by pre-eclampsia, a syndrome arising from defective placentation. Controlling placentation are maternal natural killer (NK) cells that use killer-cell immunoglobulin-like receptor (KIR) to recognize the fetal HLA-C molecules on invading trophoblast. We analyzed genetic polymorphisms of maternal KIR and fetal HLA-C in 484 normal and 254 pre-eclamptic pregnancies at Mulago Hospital, Kampala, Uganda. The combination of maternal KIR AA genotypes and fetal HLA-C alleles encoding the C2 epitope associates with pre-eclampsia [P = 0.0318, odds ratio (OR) = 1.49]. The KIR genes associated with protection are located in centromeric KIR B regions that are unique to sub-Saharan African populations and contain the KIR2DS5 and KIR2DL1 genes (P = 0.0095, OR = 0.59). By contrast, telomeric KIR B genes protect Europeans against pre-eclampsia. Thus, different KIR B regions protect sub-Saharan Africans and Europeans from pre-eclampsia, whereas in both populations, the KIR AA genotype is a risk factor for the syndrome. These results emphasize the importance of undertaking genetic studies of pregnancy disorders in African populations with the potential to provide biological insights not available from studies restricted to European populations.

scholarly journals The Extent and Impact of Variation in ADME Genes in Sub-Saharan African Populations

2021 ◽  
Vol 12 ◽  
Author(s):  
Jorge E. B. da Rocha ◽  
Houcemeddine Othman ◽  
Gerrit Botha ◽  
Laura Cottino ◽  
David Twesigomwe ◽  
...  
Keyword(s):  
Full Range ◽  
High Impact ◽  
African Population ◽  
High Coverage ◽  
Gene Variation ◽  
Research Bias ◽  
African Populations ◽  
Population Cluster ◽  
Sub Saharan ◽  
European Populations

Introduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied—which has implications for drug safety and effective use in Africa.Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., &gt;10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations.Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations.

scholarly journals Prevalence of hypertensive disorders of pregnancy and pregnancy outcomes in Sub-Saharan Africa: A systematic review and meta-analysis

2020 ◽  
Vol 16 ◽  
pp. 174550652097310
Author(s):  
Kasiye Shiferaw Gemechu ◽  
Nega Assefa ◽  
Bizatu Mengistie
Keyword(s):  
Confidence Interval ◽  
Maternal Mortality ◽  
Pregnancy Outcomes ◽  
Odds Ratio ◽  
Meta Analysis ◽  
Sub Saharan Africa ◽  
Hypertensive Disorders Of Pregnancy ◽  
Hypertensive Disorders ◽  
Pooled Prevalence ◽  
Sub Saharan

Hypertensive disorders of pregnancy are one of the leading causes of poor pregnancy outcomes and are associated with increased rates of maternal mortality, preterm birth, small for gestational age newborns, stillbirth, and neonatal death. The overall and type-specific prevalence of hypertensive disorders of pregnancy and associated pregnancy outcomes are unknown in Sub-Saharan Africa. Therefore, this review aimed to identify the prevalence of hypertensive disorders of pregnancy and associated pregnancy outcomes in Sub-Saharan Africa. A systematic review and meta-analysis were conducted on observational facility-based studies irrespective of publication status, sample size, language, and follow-up duration from 19 countries between the years 2000 and 2018 in Sub-Saharan Africa. A review of studies using PubMed, EMBASE, African Index Medicus, and African Journals Online was completed with independent extraction of studies by review authors using the predefined inclusion criteria. Quality and risk of bias of individual studies were assessed using the Joanna Briggs Institute Checklist. Random effects model was used to estimate the pooled prevalence of hypertensive disorders of pregnancy and type-specific hypertensive disorders of pregnancy. A pooled adjusted odds ratio with 95% confidence interval for each study was calculated using comprehensive meta-analysis version 2 software to estimate the association of hypertensive disorders of pregnancy and its outcomes. The existence of heterogeneity was assessed using I2 and its corresponding P value. We assessed the presence of publication bias using the Egger’s test. Subgroup analysis was performed to assess the potential effect of variables, and a sensitivity analysis was conducted to assess any undue influence from studies. The analysis included 70 studies. The pooled prevalence of hypertensive disorders of pregnancy (all types combined), chronic hypertension, gestational hypertension, preeclampsia, and eclampsia were 8% (95% confidence interval = [5, 10]), 0.9% (95% confidence interval = [0.4, 1.8]), 4.1% (95% confidence interval = [2.4, 7]), 4.1% (95% confidence interval = [3.2, 5.1]), and 1.5% (95% confidence interval = [1, 2]), respectively. Compared with normotensive pregnant or postpartum women, women with hypertensive disorders of pregnancy were associated with increased risk of maternal mortality, odds ratio = 17 (95% confidence interval = [9.6, 28.8]); cesarean section, odds ratio = 3.1 (95% confidence interval = [1.7, 5.6]); perinatal mortality, odds ratio = 8.2 (95% confidence interval = [2.8, 24]); low birth weight, odds ratio = 3.2 (95% confidence interval = [2, 5]); and preterm delivery, odds ratio = 7.8 (95% confidence interval = [2.5, 25.3]) according to this analysis. The pooled prevalence of hypertensive disorders of pregnancy was high in Sub-Saharan Africa compared to those reported from other regions. Pregnant or postpartum women with hypertensive disorders of pregnancy have increased risk of maternal mortality, cesarean section, preterm delivery, perinatal mortality, and low birth weight newborn. Therefore, creating awareness of the risks of hypertensive disorders of pregnancy is essential. Pregnant women with hypertensive disorders need due attention to manage appropriately and more importantly to have favorable outcomes in this population.

The 20210 A Allele of the Prothrombin Gene Is a Common Risk Factor among Swedish Outpatients with Verified Deep Venous Thrombosis

1997 ◽  
Vol 78 (03) ◽  
pp. 0990-0992 ◽  
Author(s):  
Andreas Hillarp ◽  
Bengt Zӧller ◽  
Peter J Svensson ◽  
Bjӧrn Dahlbäck
Keyword(s):  
Risk Factor ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Odds Ratio ◽  
Untranslated Region ◽  
Control Group ◽  
Common Risk Factor ◽  
Apc Resistance ◽  
Healthy Control ◽  
Prothrombin Gene

SummaryA dimorphism in the 3’-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis (1). We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% Cl, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% Cl, 1.1 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.

Prevalence of Factor V Leiden Mutation in Non-European Populations

1997 ◽  
Vol 77 (02) ◽  
pp. 329-331 ◽  
Author(s):  
Guglielmina Pepe ◽  
Olga Rickards ◽  
Olga Camacho Vanegas ◽  
Tamara Brunelli ◽  
Anna Maria Gori ◽  
...  
Keyword(s):  
Factor V Leiden ◽  
Indirect Evidence ◽  
Factor V ◽  
Factor V Leiden Mutation ◽  
The World ◽  
Fv Leiden ◽  
Sub Saharan ◽  
Low Prevalence ◽  
European Populations ◽  
Apparently Healthy

SummaryA difference in the prevalence of venous thromboembolism (TE) in major human groups has been described and an uneven distribution of FV Leiden mutation over the world has recently been reported.We investigated FV Leiden mutation in 584 apparently healthy sub#jects mostly from populations different from those previously investi#gated: 170 Europeans (Spanish, Italians), 101 sub-saharan Africans (Fon, Bariba, Berba, Dendi), 115 Asians (Indonesians, Chinese, Tharus), 57 Amerindians (Cayapa), 84 Afroamericans (Rio Cayapa, Viche), and 57 Ethiopians (Amhara, Oromo).The mutation was detected in only 1/115 Asian (Tharu) and in 5/170 Europeans (4 Italians, 1 Spanish).These data confirm that in non-Europeans the prevalence of FV mutation is at least 7 times lower than in Europeans and provide indirect evidence of a low prevalence not only of the FV Leiden gene but also of other genes leading to more severe thrombophilia. Finally, findings from the literature together with those pertaining to this study clearly show a marked heterogeneity among Europeans.

scholarly journals Estimating the burden of cardiovascular risk in community dwellers over 40 years old in South Africa, Kenya, Burkina Faso and Ghana

2021 ◽  
Vol 6 (1) ◽  
pp. e003499
Author(s):  
Ryan G Wagner ◽  
Nigel J Crowther ◽  
Lisa K Micklesfield ◽  
Palwende Romauld Boua ◽  
Engelbert A Nonterah ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
South African ◽  
Sub Saharan Africa ◽  
African Countries ◽  
Cvd Risk ◽  
Genomic Studies ◽  
Sub Saharan ◽  
Context Specific ◽  
The Impact

IntroductionCardiovascular disease (CVD) risk factors are increasing in sub-Saharan Africa. The impact of these risk factors on future CVD outcomes and burden is poorly understood. We examined the magnitude of modifiable risk factors, estimated future CVD risk and compared results between three commonly used 10-year CVD risk factor algorithms and their variants in four African countries.MethodsIn the Africa-Wits-INDEPTH partnership for Genomic studies (the AWI-Gen Study), 10 349 randomly sampled individuals aged 40–60 years from six sites participated in a survey, with blood pressure, blood glucose and lipid levels measured. Using these data, 10-year CVD risk estimates using Framingham, Globorisk and WHO-CVD and their office-based variants were generated. Differences in future CVD risk and results by algorithm are described using kappa and coefficients to examine agreement and correlations, respectively.ResultsThe 10-year CVD risk across all participants in all sites varied from 2.6% (95% CI: 1.6% to 4.1%) using the WHO-CVD lab algorithm to 6.5% (95% CI: 3.7% to 11.4%) using the Framingham office algorithm, with substantial differences in risk between sites. The highest risk was in South African settings (in urban Soweto: 8.9% (IQR: 5.3–15.3)). Agreement between algorithms was low to moderate (kappa from 0.03 to 0.55) and correlations ranged between 0.28 and 0.70. Depending on the algorithm used, those at high risk (defined as risk of 10-year CVD event >20%) who were under treatment for a modifiable risk factor ranged from 19.2% to 33.9%, with substantial variation by both sex and site.ConclusionThe African sites in this study are at different stages of an ongoing epidemiological transition as evidenced by both risk factor levels and estimated 10-year CVD risk. There is low correlation and disparate levels of population risk, predicted by different risk algorithms, within sites. Validating existing risk algorithms or designing context-specific 10-year CVD risk algorithms is essential for accurately defining population risk and targeting national policies and individual CVD treatment on the African continent.

scholarly journals The Association of Familial Hypertension and Risk of Gestational Hypertension and Preeclampsia

2021 ◽  
Vol 18 (13) ◽  
pp. 7045
Author(s):  
Małgorzata Lewandowska
Keyword(s):  
Risk Factor ◽  
Pregnant Women ◽  
Odds Ratio ◽  
Independent Risk Factor ◽  
Gestational Hypertension ◽  
First Trimester ◽  
Chronic Hypertension ◽  
Modifiable Factors ◽  
The Family ◽  
Maternal Hypertension

It has not been established how history of hypertension in the father or mother of pregnant women, combined with obesity or smoking, affects the risk of main forms of pregnancy-induced hypertension. A cohort of 912 pregnant women, recruited in the first trimester, was assessed; 113 (12.4%) women developed gestational hypertension (GH), 24 (2.6%) developed preeclampsia (PE) and 775 women remained normotensive (a control group). Multiple logistic regression was used to calculate adjusted odds ratios (AOR) (and 95% confidence intervals) of GH and PE for chronic hypertension in the father or mother of pregnant women. Some differences were discovered. (1) Paternal hypertension (vs. absence of hypertension in the family) was an independent risk factor for GH (AOR-a = 1.98 (1.2–3.28), p = 0.008). This odds ratio increased in pregnant women who smoked in the first trimester (AOR-a = 4.71 (1.01–21.96); p = 0.048) or smoked before pregnancy (AOR-a = 3.15 (1.16–8.54); p = 0.024), or had pre-pregnancy overweight (AOR-a = 2.67 (1.02–7.02); p = 0.046). (2) Maternal hypertension (vs. absence of hypertension in the family) was an independent risk factor for preeclampsia (PE) (AOR-a = 3.26 (1.3–8.16); p = 0.012). This odds ratio increased in the obese women (AOR-a = 6.51 (1.05–40.25); p = 0.044) and (paradoxically) in women who had never smoked (AOR-a = 5.31 (1.91–14.8); p = 0.001). Conclusions: Chronic hypertension in the father or mother affected the risk of preeclampsia and gestational hypertension in different ways. Modifiable factors (overweight/obesity and smoking) may exacerbate the relationships in question, however, paradoxically, beneficial effects of smoking for preeclampsia risk are also possible. Importantly, paternal and maternal hypertension were not independent risk factors for GH/PE in a subgroup of women with normal body mass index (BMI).

Prospective Analysis after Coronary-artery Bypass Grafting: Platelet GP IIIa Polymorphism (HPA-1b /PlA2) Is a Risk Factor for Bypass Occlusion, Myocardial Infarction, and Death

2000 ◽  
Vol 83 (03) ◽  
pp. 404-407 ◽  
Author(s):  
Michael Klein ◽  
Hans Dauben ◽  
Christiane Moser ◽  
Emmeran Gams ◽  
Rüdiger Scharf ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Risk Factor ◽  
Coronary Artery ◽  
Odds Ratio ◽  
Bypass Surgery ◽  
Artery Bypass ◽  
Bypass Grafting ◽  
Hereditary Risk ◽  
Artery Disease

SummaryRecently, we have demonstrated that human platelet antigen 1b (HPA-1b or PlA2) is a hereditary risk factor for platelet thrombogenicity leading to premature myocardial infarction in preexisting coronary artery disease. However, HPA-1b does not represent a risk factor for coronary artery disease itself. The aim of our present study was to evaluate the role of HPA-1b on the outcome in patients after coronaryartery bypass surgery. We prospectively determined the HPA-1 genotype in 261 consecutive patients prior to saphenous-vein coronaryartery bypass grafting. The patients were followed for one year. Among patients with bypass occlusion, myocardial infarction, or death more than 30 days after surgery, the prevalence of HPA-1b was significantly higher than among patients without postoperative complications (60 percent, 6/10, vs. 24 percent, 58/241, p <0.05, odds ratio 4.7). Using a stepwise logistic regression analysis with the variables HPA1b, age, sex, body mass index, smoking (pack-years), hypertension, diabetes, cholesterol and triglyceride concentration, only HPA-1b had a significant association with bypass occlusion, myocardial infarction, or death after bypass surgery (p = 0.019, odds ratio 4.7). This study shows that HPA-1b is a hereditary risk factor for bypass occlusion, myocardial infarction, or death in patients after coronary-artery bypass surgery.

scholarly journals Prevalence and Predictors of Undiagnosed Hypertension in an Apparently Healthy Western Indian Population

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Anand N. Shukla ◽  
Tarun Madan ◽  
Bhavesh M. Thakkar ◽  
Meena M. Parmar ◽  
Komal H. Shah
Keyword(s):  
Blood Pressure ◽  
Risk Factor ◽  
Cardiovascular Diseases ◽  
Odds Ratio ◽  
Indian Population ◽  
Total Population ◽  
Undiagnosed Hypertension ◽  
History Of ◽  
Major Illness ◽  
Apparently Healthy

This epidemiological study was designed to evaluate the prevalence of undetected hypertension in an apparently healthy western Indian population having no history of major illness. 3629 individuals of ≥18 years of age were included in the study. Hypertension (HTN) was defined as systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg and prehypertension (PHTN) as SBP ≥ 120–139 mmHg or DBP ≥ 80–89 mmHg, but without HTN. The prevalence of undiagnosed HTN in the total population was 26% and was 11% and 40% in the young (≤40-year) and old (>40-year) populations, respectively. The prevalence of PHTN, 40% in the overall population, was nearly the same in the young (39%) and the old population (42%). The risk factor most strongly associated with PHTN and HTN was obesity, showing the highest odds ratio in the overall (PHTN 2.14; 95% CI 1.20–3.81; HTN 2.72; 95% CI 1.53–4.85), the young (PHTN 2.29; 95% CI 1.25–4.21; HTN 2.92; 95% CI 1.59–5.35), and the old (PHTN 1.13; 95% CI 0.65–1.96; HTN 1.38; 95% CI 0.79–2.4) populations. Hypertension is a major risk factor for cardiovascular diseases which must not be ignored, especially in the western Indian population.

scholarly journals Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics

2008 ◽  
Vol 124 (2) ◽  
pp. 195-195
Author(s):  
Giorgio Sirugo ◽  
Branwen J. Hennig ◽  
Adebowale A. Adeyemo ◽  
Alice Matimba ◽  
Melanie J. Newport ◽  
...  
Keyword(s):  
Disease Susceptibility ◽  
Genetic Studies ◽  
African Populations
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