Browsing by Author "Tiwari H. K."

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African Ancestry, APOL1, candidate genes, CDKN2A/CDKN2B, HDAC9, small vessel disease, stroke, West Africa
(John Wiley & Sons Ltd, 2017) Akinyemi R.; Tiwari H. K.; Arnett D. K.; Ovbiagele B.; Irvin M. R.; Wahab K.; Sarfo F.; Srinivasasainagendra V.; Adeoye A.; Perry R. T.; Akpalu A.; Jenkins C.; Arulogun O.; Gebregziabher M.; Owolabi L.; Obiako R.; Sanya E.; Komolafe M.; Fawale M.; Adebayo P.; Osaigbovo G.; Sunmonu T.; Olowoyo P.; Chukwuonye I.; Obiabo Y.; Onoja A.; Akinyemi J.; Ogbole G.; Melikam S.; Saulson R.; Owolabi M.
Objective: Worldwide, the highest frequencies of APOL1-associated kidney variants are found in indigenous West Africans among whom small vessel disease (SVD) is chemic stroke is the most common stroke phenotype. The objective of this study was to investigate the association and effect sizes of 23 selected SNPs in 14 genes of relevance, including the APOL1 G1 variants, with the occurrence of SVD ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Materials and Methods: Cases were consecutively recruited consenting adults (aged 18 years or older) with neuroimaging—confirmed first clinical stroke. Stroke-free controls were ascertained using a locally validated version of the Questionnaire for Verifying Stroke-Free Status (QVSFS). Logistic regression models adjusting for known vascular risk factors were fitted to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 154) of SVD ischemic stroke and stroke-free (N = 483) controls. Results: Apolipoprotein L1 (APOL1) rs73885319 (OR = 1.52; CI: 1.09-2.13, P value = .013), rs2383207 in CDKN2A/CDKN2B (OR = 3.08; CI: 1.15-8.26, P – value = .026) and rs2107595 (OR = 1.70; CI: 1.12-2.60, P-value = .014) and rs28688791 (OR = 1.52; CI: 1.03-2.26, P-value = .036) in HDAC9 gene were associated with SVD stroke at 0.05 significance level. Polymorphisms in other genes did not show significant associations. Conclusion: This is the first report of a specific association of APOL1 with a stroke subtype. Further research is needed to confirm these initial findings and deepen understanding of the genetics of stroke in people of African ancestry with possible implications for other ancestries as all humans originated from Africa
Differential impact of risk factors on stroke occurrence among men versus women in West Africa The SIREN Study
(American Heart Association, Inc., 2019) Akpalu A.; Gebregziabher M.; Ovbiagele B.; Sarfo F.; Iheonye H.; Akinyemi R.; Akpa O.; Tiwari H. K.; Arnett D.; Wahab K.; Lackland D.; Abiodun A.; Ogbole G.; Jenkins C.; Arulogun O.; Akpalu J.; Obiako R.; Olowoyo P.; Fawale M.; Komolafe M.; Osaigbovo G.; Obiabo Y.; Chukwuonye I.; Owolabi L.; Adebayo P.; Sunmonu T.; Owolabi M.
Background and Purpose—The interplay between sex and the dominant risk factors for stroke occurrence in sub-Saharan Africa has not been clearly delineated. We compared the effect sizes of risk factors of stroke by sex among West Africans. Methods—SIREN study (Stroke Investigative Research and Educational Networks) is a case-control study conducted at 15 sites in Ghana and Nigeria. Cases were adults aged >18 years with computerized tomography/magnetic resonance imaging confirmed stroke, and controls were age- and sex-matched stroke-free adults. Comprehensive evaluation for vascular, lifestyle, and psychosocial factors was performed using validated tools. We used conditional logistic regression to estimate odds ratios and reported risk factor specific and composite population attributable risks with 95% CIs. Results—Of the 2118 stroke cases, 1193 (56.3%) were males. The mean±SD age of males was 58.1±13.2 versus 60.15±14.53 years among females. Shared modifiable risk factors for stroke with adjusted odds ratios (95% CI) among females versus males, respectively, were hypertension [29.95 (12.49–71.77) versus 16.1 0(9.19–28.19)], dyslipidemia [2.08 (1.42–3.06) versus 1.83 (1.29–2.59)], diabetes mellitus [3.18 (2.11–4.78) versus 2.19 (1.53–3.15)], stress [2.34 (1.48–3.67) versus 1.61 (1.07–2.43)], and low consumption of green leafy vegetables [2.92 (1.89–4.50) versus 2.00 (1.33–3.00)]. However, salt intake and income were significantly different between males and females. Six modifiable factors had a combined population attributable risk of 99.1% (98.3%–99.6%) among females with 9 factors accounting for 97.2% (94.9%–98.7%) among males. Hemorrhagic stroke was more common among males (36.0%) than among females (27.6%), but stroke was less severe among males than females. Conclusions—Overall, risk factors for stroke occurrence are commonly shared by both sexes in West Africa favoring concerted interventions for stroke prevention in the region.
Exploring overlaps between the genomic and environmental determinants of LVH and stroke
(Elsevier Ltd, 2017) Adeoye A. M.; Ovbiagele B.; Kolo P.; Appiah L.; Ajek A.; Adebayo O.; Sarfo F.; Akinyemi J.; Adekunle G.; Agyekum F.; Shidali V.; Ogah O.; Lackland D.; Gebregziabher M.; Arnett D.; Tiwari H. K.; Akinyemi R.; Olagoke O. O.; Oguntade A. S.; Olunuga T.; Uwanruochi K.; Jenkins C.; Adadey P.; Iheonye H.; Owolabi L.; Obiako R.; Akinjopo S.; Armstrong K.; Akpalu A.; Fakunle A.; Saulson R.; Aridegbe M.; Olowoyo P.; Osaigbovo G.; Akpa O.
Background: Whether left ventricular hypertrophy (LVH) is determined by similar genomic and environmental risk factors with stroke, or is simply an intermediate stroke marker, is unknown. Objectives: We present a research plan and preliminary findings to explore the overlap in the genomic and environmental determinants of LVH and stroke among Africans participating in the SIREN (Stroke Investigative Research and Education Network) study. Methods: SIREN is a transnational, multicenter study involving acute stroke patients and age-, ethnicity-, and sex-matched control subjects recruited from 9 sites in Ghana and Nigeria. Genomic and environmental risk factors and other relevant phenotypes for stroke and LVH are being collected and compared using standard techniques. Results: This preliminary analysis included only 725 stroke patients (mean age 59.1 13.2 years; 54.3% male). Fifty-five percent of the stroke subjects had LVH with greater proportion among women (51.6% vs. 48.4%; p < 0.001). Those with LVH were younger (57.9 12.8 vs. 60.6 13.4; p ¼ 0.006) and had higher mean systolic and diastolic blood pressure (167.1/99.5 mm Hg vs 151.7/90.6 mm Hg; p < 0.001). Uncontrolled blood pressure at presentation was prevalent in subjects with LVH (76.2% vs. 57.7%; p < 0.001). Significant independent predictors of LVH were age 90 mm Hg (AOR: 2.10; 95% CI: 1.39 to 3.19; p < 0.001). Conclusions: The prevalence of LVH was high among stroke patients especially the younger ones, suggesting a genetic component to LVH. Hypertension was a major modifiable risk factor for stroke as well as LVH. It is envisaged that the SIREN project will elucidate polygenic overlap (if present) between LVH and stroke among Africans, thereby defining the role of LVH as a putative intermediate cardiovascular phenotype and therapeutic target to inform interventions to reduce stroke risk in populations of African ancestry
Interleukin–6 (IL-6) rs1800796 and cyclin dependent kinase inhibitor (CDKN2A/CDKN2B) rs2383207 are associated with ischemic stroke in indigenous West African Men
(Elvsevier B. V, 2017) Akinyemi R.; Arnett D. K.; Tiwari H. K.; Ovbiagele B.; Sarfo F.; Srinivasasainagendra V.; Irvin M. R.; Adeoye A.; Perry R. T.; Akpalu A.; Jenkins C.; Owolabi L.; Obiako R.; Wahab K.; Sanya E.; Komolafe M.; Fawale M.; Adebayo P.; Osaigbovo G.; Sunmonu T.; Olowoyo P.; Chukwuonye I.; Obiabo Y.; Akpa O.; Melikam S.; Saulson R.; Kalaria R.; Ogunniyi A.; Owolabi M.
Background: Inherited genetic variations offer a possible explanation for the observed peculiarities of stroke in sub - Saharan African populations. Interleukin–6 polymorphisms have been previously associated with ischemic stroke in some non-African populations. Aim: Herein we investigated, for the first time, the association of genetic polymorphisms of IL-6, CDKN2A CDKN2B and other genes with ischemic stroke among indigenous West African participants in the Stroke Investigative Research and Education Network (SIREN) Study. Methods: Twenty-three previously identified single nucleotide polymorphisms (SNPs) in 14 genes of relevance to the neurobiology of ischemic stroke were investigated. Logistic regression models adjusting for known cardio vascular disease risk factors were constructed to assess the associations of the 23 SNPs in rigorously phenotyped cases (N = 429) of ischemic stroke (Men = 198; Women = 231) and stroke– free (N = 483) controls (Men = 236; Women = 247). Results: Interleukin-6 (IL6) rs1800796 (C minor allele; frequency: West Africans = 8.6%) was significantly associated with ischemic stroke in men (OR = 2.006, 95% CI = [1.065, 3.777], p = 0.031) with hypertension in the model but not in women. In addition, rs2383207 in CDKN2A/CDKN2B (minor allele A with frequency: West Africans = 1.7%) was also associated with ischemic stroke in men (OR = 2.550, 95% CI = [1.027, 6.331], p = 0.044) with primary covariates in the model, but not in women. Polymorphisms in other genes did not show significant association with ischemic stroke.