Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study
dc.contributor.author | Miguel Yanes, José María De | |
dc.contributor.author | Porneala, Bianca | |
dc.contributor.author | Pencina, Michael | |
dc.contributor.author | Fox, Caroline | |
dc.contributor.author | Florez, Jose | |
dc.contributor.author | Siscovick, David | |
dc.contributor.author | Dupuis, Josée | |
dc.contributor.author | Meigs, James | |
dc.date.accessioned | 2024-01-12T09:19:23Z | |
dc.date.available | 2024-01-12T09:19:23Z | |
dc.date.issued | 2013 | |
dc.description.abstract | Objective: To test whether pancreatic beta-cell genetic frailty and hypertension (HTN) interact in their associations with change over time in fasting glucose (ΔFG) or type 2 diabetes mellitus (T2D) risk. Methods and results: We pooled data from 3471 Framingham Offspring Study participants into six ∼4-year periods (15 852 person-examinations; mean age 52; 54% women). We defined two genetic exposures reflecting beta-cell genetic risk burden: single nucleotide polymorphism (SNP) score counts of fasting glucose-associated and T2D-associated risk alleles at 16 and 33 putative beta-cell loci, respectively; and three HTN exposures: HTN versus no-HTN; treated versus untreated HTN; and five mutually exclusive antihypertensive categories (beta-blockers, thiazides, renin-angiotensin system agents, combinations, others) versus untreated HTN. We tested ∼4-year mean ΔFG or odds of T2D by per-risk allele score change and HTN category, seeking genetic score-by-HTN interaction. Genetic scores increased ∼4-year ΔFG (0.6 mg/dl per-risk allele; P = 8.9 × 10(-16)) and T2D-risk (∼17% per-risk allele; P = 2.1 × 10(-7)). As compared to no-HTN, HTN conferred higher ΔFG (2.6 versus 1.7 mg/dl; P < 0.0001) and T2D-risk [odds ratio (OR) = 2.9, 95% confidence interval (CI) 2.8-3.0; P < 0.0001]. As compared to untreated HTN, treated HTN conferred higher ΔFG (3.4 versus 3.0 mg/dl; P < 0.0001) and T2D-risk (OR = 1.4, 95% CI 1.3-1.5; P = 0.02). Beta-blockers (OR = 1.6, 95% CI 1.1-2.4), combinations (OR = 1.6, 95% CI 1.1-2.5), and others (OR = 2.0, 95% CI 1.4-2.9) increased T2D-risk (all P < 0.02). In joint models including interaction terms, all genetic score-by-HTN interaction terms were P value greater than 0.05. In joint models without interaction, fasting glucose-SNP or T2D-SNP genetic scores (both P < 0.001) and HTN (P < 0.0001) independently increased ΔFG or T2D-risk. Conclusion: HTN, HTN treatment, and common fasting glucose-SNP genetic score/T2D-SNP genetic score independently predicted ΔFG and T2D incidence, but did not modify each other's association with ΔFG or T2D risk. | |
dc.description.department | Depto. de Medicina | |
dc.description.faculty | Fac. de Medicina | |
dc.description.refereed | TRUE | |
dc.description.sponsorship | National Institute for Diabetes and Digestive and Kidney Diseases | |
dc.description.sponsorship | National Institutes of Health | |
dc.description.sponsorship | Boston University School of Medicine | |
dc.description.sponsorship | SNP Health Association Resource | |
dc.description.sponsorship | Affimetrix | |
dc.description.sponsorship | Boston Medical Center | |
dc.description.status | pub | |
dc.identifier.citation | de Miguel-Yanes JM, Porneala B, Pencina MJ, Fox CS, Florez JC, Siscovick DS, Dupuis J, Meigs JB. Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study. J Hypertens. 2013 May;31(5):1001-9 | |
dc.identifier.doi | 10.1097/HJH.0b013e32835f5a83 | |
dc.identifier.issn | 0263-6352 | |
dc.identifier.officialurl | htttps://doi.org/10.1097/HJH.0b013e32835f5a83 | |
dc.identifier.relatedurl | https://pubmed.ncbi.nlm.nih.gov/23425704/ | |
dc.identifier.uri | https://hdl.handle.net/20.500.14352/92681 | |
dc.issue.number | 5 | |
dc.journal.title | Journal of Hypertension | |
dc.language.iso | eng | |
dc.page.final | 1009 | |
dc.page.initial | 1001 | |
dc.publisher | Lippincott, Williams & Wilkins | |
dc.rights.accessRights | restricted access | |
dc.subject.cdu | 616.1/.9 | |
dc.subject.keyword | Fasting glucose | |
dc.subject.keyword | Framingham | |
dc.subject.keyword | Genes | |
dc.subject.keyword | Genetic risk scores | |
dc.subject.keyword | Hypertension | |
dc.subject.keyword | Hypertension treatment | |
dc.subject.ucm | Medicina interna | |
dc.subject.unesco | 3205 Medicina Interna | |
dc.title | Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk: the Framingham Offspring Study | |
dc.type | journal article | |
dc.type.hasVersion | VoR | |
dc.volume.number | 31 | |
dspace.entity.type | Publication | |
relation.isAuthorOfPublication | 7ed9b0a8-df93-404b-b68b-876caee32ec8 | |
relation.isAuthorOfPublication.latestForDiscovery | 7ed9b0a8-df93-404b-b68b-876caee32ec8 |
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