APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke

Akinyemi, Rufus; Tiwari, Hemant K.; Arnett, Donna K.; Ovbiagele, Bruce; Irvin, Marguerite R.; Wahab, Kolawole; Srinivasasainagendra, Vinodh; Adeoye, Abiodun M.; Perry, Rodney T.; Akpalu, Albert; Jenkins, Carolyn; Arulogun, Oyedunni; Gebregziabher, Mulugeta; Owolabi, Lukman; Obiako, Reginald; Sanya, Emmanuel; Komolafe, Morenikeji; Fawale, Bimbo; Adebayo, Philip; Osaigbovo, Godwin; Sunmonu, Taofiki; Olowoyo, Paul; Chukwuonye, Innocent Ijezie; Obiabo, Yahaya; Akpa, Onoja; Akinyemi, Joshua; Ogbole, Godwin; Melikam, Sylvia; Saulson, Raelle; Owolabi, Mayowa

doi:10.1111/ane.12847

Cited by 32 publications

(34 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously reported that blood pressure and glycemic control are poor among Ghanaians seeking health care in medical facilities . We have also shown earlier that CKD independently predicts incident stroke among Ghanaians with diabetes and hypertension and that this increased risk may have genetic underpinnings . In this regard, interventions that would enhance adherence to medications such as use of m‐health may be useful to explore in our settings .…”

Section: Discussionmentioning

confidence: 87%

“…45 We have also shown earlier that CKD independently predicts incident stroke among Ghanaians with diabetes and hypertension 46 and that this increased risk may have genetic underpinnings. 47,48 In this regard, interventions that would enhance adherence to medications such as use of m-health may be useful to explore in our settings. 49,50 Proteinuria should be treated with high-dose ACE-I or ARBs but with extreme caution in combination due to high-risk hyperkalemia, hypotension, and worsening renal function.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prevalence and predictors of chronic kidney disease among Ghanaian patients with hypertension and diabetes mellitus: A multicenter cross‐sectional study

Tannor

Sarfo

Mobula

et al. 2019

J of Clinical Hypertension

View full text Add to dashboard Cite

The burden of chronic kidney disease (CKD) is rapidly rising in developing countries due to astronomical increases in key risk factors including hypertension and diabetes. We sought to assess the burden and predictors of CKD among Ghanaians with hypertension and/or diabetes mellitus in a multicenter hospital‐based study. We conducted a cross‐sectional study in the Ghana Access and Affordability Program (GAAP) involving adults with hypertension only (HPT), hypertension with diabetes mellitus (HPT + DM), and diabetes mellitus only (DM) in 5 health facilities in Ghana. A structured questionnaire was administered to collect data on demographic variables, medical history, and clinical examination. Serum creatinine and proteinuria were measured, and estimated glomerular filtration rate derived using the CKD‐EPI formula. A multivariable logistic regression model was used to identify factors associated with CKD. A total of 2781 (84.4%) of 3294 participants had serum creatinine and proteinuria data available for analysis. The prevalence of CKD was 242 (28.5%) among participants with both DM and HPT, 417 (26.3%) among participants with HPT, and 56 (16.1%) among those with DM alone. Predictors of CKD were increasing age aOR 1.26 (1.17‐1.36), low educational level aOR 1.7 (1.23‐2.35), duration of HPT OR, 1.02 (1.01‐1.04), and use of herbal medications aOR 1.39 (1.10‐1.75). Female gender was protective of CKD aOR 0.75 (0.62‐0.92). Among patients with DM, increasing age and systolic blood pressure were associated with CKD. There is high prevalence of CKD among DM and hypertension patients in Ghana. Optimizing blood pressure control and limiting the use of herbal preparations may mitigate CKD occurrence in high cardiovascular risk populations in developing countries.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Prevalence and predictors of chronic kidney disease among Ghanaian patients with hypertension and diabetes mellitus: A multicenter cross‐sectional study

Tannor

Sarfo

Mobula

et al. 2019

J of Clinical Hypertension

View full text Add to dashboard Cite

show abstract

“…Similarly, in the LAA subtype, the interaction between FER rs10447248 and NOS1 rs2139733 increased the risk of ischemic stroke risk. NOS1 is actively involved in the inflammatory pathway where the adiponectin level associated with FER variants is also closely involved (Akinyemi et al, 2018; Casas et al, 2019; Huang, Jin, & Yang, 2018; Qi et al, 2011). Ischemic stroke has been reported to be associated with inflammation in disease etiology (Gairolla, Kler, Modi, & Khurana, 2017), the interaction identified between FER and NOS1 might enrich evidence of the genetic understanding of ischemic stroke etiology.…”

Section: Discussionmentioning

confidence: 99%

Exploring gene–gene interaction in family‐based data with an unsupervised machine learning method: EPISFA

Xiao

Wang

Liu

et al. 2020

Genetic Epidemiology

View full text Add to dashboard Cite

Gene–gene interaction (G × G) is thought to fill the gap between the estimated heritability of complex diseases and the limited genetic proportion explained by identified single‐nucleotide polymorphisms. The current tools for exploring G × G were often developed for case‐control designs with less considerations for their applications in families. Family‐based studies are robust against bias led from population stratification in genetic studies and helpful in understanding G × G. We proposed a new algorithm epistasis sparse factor analysis (EPISFA) and epistasis sparse factor analysis for linkage disequilibrium (EPISFA‐LD) based on unsupervised machine learning to screen G × G. Extensive simulations were performed to compare EPISFA/EPISFA‐LD with a classical family‐based algorithm FAM‐MDR (family‐based multifactor dimensionality reduction). The results showed that EPISFA/EPISFA‐LD is a tool of both high power and computational efficiency that could be applied in family designs and is applicable within high‐dimensionality datasets. Finally, we applied EPISFA/EPISFA‐LD to a real dataset drawn from the Fangshan/family‐based Ischemic Stroke Study in China. Five pairs of G × G were discovered by EPISFA/EPISFA‐LD, including three pairs verified by other algorithms (FAM‐MDR and logistic), and an additional two pairs uniquely identified by EPISFA/EPISFA‐LD only. The results from EPISFA might offer new insights for understanding the genetic etiology of complex diseases. EPISFA/EPISFA‐LD was implemented in R. All relevant source code as well as simulated data could be freely downloaded from https://github.com/doublexism/episfa.

show abstract

“…There is a close association between cerebral and glomerular small vessel diseases and between brain small vessel disease and hemorrhage. Recently an association of APOL1 rs73885319 with small vessel type stroke in a cohort of indigenous African stroke patients was reported . For this reason an association between the APOL1 variants and stroke in SCD populations of African ancestry should be explored. Haptoglobin Haplotype: SCD is a hemolytic anemia, and large amounts of free hemoglobin are released from red blood cell lysis.…”

mentioning

confidence: 99%

“…H‐1 is more efficient at presenting free Hb to the macrophage, which takes it out of circulation. Individuals with the H2 allelle (especially the H2‐2 genotype) develop a more powerful immune response to infections . The problem is that the heightened immune response may be a distinct disadvantage for patients with a systemic illness.…”

mentioning

confidence: 99%

New approaches to genetic predisposition for hemorrhagic stroke in sickle cell disease

Adams

Akinyemi

Owolabi

et al. 2018

J of Clinical Hypertension

View full text Add to dashboard Cite

Hypertension has not traditionally been considered a significant problem in sickle cell disease (SCD) but that view is changing. 1 In the general population hypertension leads, among other things, to small vessel disease of the kidney and brain and to intracerebral hemorrhage, which are important complications of SCD. Although SCD is the most common monogenetic disease, its wide phenotypic variation has, for the most part, eluded satisfactory explanation. Except for coinheritance of alpha thalassemia and certain genes that affect fetal hemoglobin production, genomic studies have not converged on clear genetic risk markers for important complications such as stroke 2 although promising candidates have recently been proposed. 3 Specific genomic risk indicators for intracranial hemorrhage have not been reported. Although first ischemic stroke has been greatly reduced by regular red cell transfusion initiated on the basis of risk stratification by transcranial Doppler ultrasound 4 (STOP Protocol) there has been no corresponding reduction in intracranial hemorrhage inSCD. 5 With increased survival and decreased burden of ischemic stroke, intracerebral hemorrhage (ICH) will become an increasingly important problem. Robust predictors could lead to targeted prevention and reduction of this important type of stroke.Our understanding of risk for hemorrhagic stroke in SCD comes primarily from the Cooperative Study of Sickle Cell Disease. 6 This was an important effort to characterize the common phenotypes including stroke (ischemic and hemorrhage) but these data are over 30 years and the hemorrhagic stroke predictive model was based on only 27 events.Transcranial Doppler ultrasound is very effective in guiding transfusion or hydroxyurea to prevent ischemic stroke but does not clearly identify those at risk for hemorrhagic stroke. The existing phenotype-based risk model from the cooperative study is not specific enough to support clinical trials. There is a critical need to modernize our research strategies to find robust models if we are to reduce hemorrhagic stroke.We propose a shift in perspective. For example, in patients without SCD, several genes have been linked to intracerebral hemorrhage. 7 Ongoing efforts are developing stroke genomics from an African perspective 8,9 including achieving a better understanding of the genomics of predisposing factors such as hypertension. 10 The H3Africa Project was established by the US National Institutes of Health and the Wellcome Trust to develop capacity in genomic research in Africa, including specific projects focusing on assessment of perceptions about public health interventions to increase awareness, early detection and prevention of SCD-related complications 11 and the Sickle Pan-African Research Consortium (SPARCO) 12 that aims to develop infrastructure for sickle cell disease research, health care, education, and training in Africa. Instead of looking at thesepatients as individuals with SCD who typically happen to be black, we believe a better approach is to view them a...

show abstract

APOL1, CDKN2A/CDKN2B, and HDAC9 polymorphisms and small vessel ischemic stroke

Cited by 32 publications

References 64 publications

Prevalence and predictors of chronic kidney disease among Ghanaian patients with hypertension and diabetes mellitus: A multicenter cross‐sectional study

Prevalence and predictors of chronic kidney disease among Ghanaian patients with hypertension and diabetes mellitus: A multicenter cross‐sectional study

Exploring gene–gene interaction in family‐based data with an unsupervised machine learning method: EPISFA

New approaches to genetic predisposition for hemorrhagic stroke in sickle cell disease

Contact Info

Product

Resources

About