J Kayima1,2, J Liang3, Y Natanzon3, J Nankabirwa4, I Ssinabulya1,2, J Nakibuuka2, A Katamba4, H Mayanja-Kizza2, A Miron5, C Li3, X Zhu3. 1. Division of Adult Cardiology, Uganda Heart Institute, Kampala, Uganda. 2. Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda. 3. Department of Epidemiology & Biostatistics, School of Medicine, Case Western Reserve University, Cleveland, Ohio. 4. Clinical Epidemiology Unit, Department of Medicine, School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda. 5. Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
Abstract
INTRODUCTION: Genetic variation may play explain some of the disparity in prevalence and control of hypertension across Sub-Saharan Africa. However, there have been very few studies to characterize genetic variation of blood pressure traits. AIM: To determine whether a set of blood pressure-associated genetic loci can be replicated among samples East African samples. METHODS: Twenty-seven blood pressures (BP)-related single nucleotide polymorphisms (SNPs) were genotyped among 2881 samples from participants in the Medical Education Partnership Initiative for Cardiovascular Disease (MEPI-CVD) survey. Associations with known BP variants were evaluated for systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) as continuous variables and for hypertension (HTN) as a binary variable. RESULTS: Eleven SNPS were associated with at least 1 BP trait (P < .05). Four SNPs; rs2004776, rs7726475, rs11837544 and rs2681492, whose nearest genes are AGT, NPR3/SUB1, PLXNC1 and ATP2B1, respectively, were associated with SBP. Six SNPs, rs2004776, rs11977526, rs11191548, rs381815, rs2681492 and rs1327235, close to AGT, IGFBP3, CYP17A1, PLEKHA7, ATP2B1 and JAG, respectively, were associated with DBP while 2 SNPs located within AGT and IGFBP-3 genes associated with HTN. For PP, 4 variants rs1458038, rs11725861, rs7726475 and rs11953630 whose corresponding genes are FGF5, CHIC2, SUB1/NPR3 and EBF1 reached significance (P < .05). Eight SNPs were replicated in the same effect direction as the parent studies. Risk scores defined using published effect sizes were significantly associated with both SBP (P = .0026) and DBP (P = .0214). CONCLUSION: The replication of multiple BP variants among East Africans suggests that these variants may have universal effects across ethnic populations.
INTRODUCTION: Genetic variation may play explain some of the disparity in prevalence and control of hypertension across Sub-Saharan Africa. However, there have been very few studies to characterize genetic variation of blood pressure traits. AIM: To determine whether a set of blood pressure-associated genetic loci can be replicated among samples East African samples. METHODS: Twenty-seven blood pressures (BP)-related single nucleotide polymorphisms (SNPs) were genotyped among 2881 samples from participants in the Medical Education Partnership Initiative for Cardiovascular Disease (MEPI-CVD) survey. Associations with known BP variants were evaluated for systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) as continuous variables and for hypertension (HTN) as a binary variable. RESULTS: Eleven SNPS were associated with at least 1 BP trait (P < .05). Four SNPs; rs2004776, rs7726475, rs11837544 and rs2681492, whose nearest genes are AGT, NPR3/SUB1, PLXNC1 and ATP2B1, respectively, were associated with SBP. Six SNPs, rs2004776, rs11977526, rs11191548, rs381815, rs2681492 and rs1327235, close to AGT, IGFBP3, CYP17A1, PLEKHA7, ATP2B1 and JAG, respectively, were associated with DBP while 2 SNPs located within AGT and IGFBP-3 genes associated with HTN. For PP, 4 variants rs1458038, rs11725861, rs7726475 and rs11953630 whose corresponding genes are FGF5, CHIC2, SUB1/NPR3 and EBF1 reached significance (P < .05). Eight SNPs were replicated in the same effect direction as the parent studies. Risk scores defined using published effect sizes were significantly associated with both SBP (P = .0026) and DBP (P = .0214). CONCLUSION: The replication of multiple BP variants among East Africans suggests that these variants may have universal effects across ethnic populations.
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