Neal S Parikh1, Nicole Dueker2, Dalila Varela3, Victor J Del Brutto4, Tatjana Rundek5, Clinton B Wright6, Ralph L Sacco7, Mitchell S V Elkind8, Jose Gutierrez3. 1. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. Electronic address: nsp2001@med.cornell.edu. 2. John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA. 3. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA. 4. Department of Neurology, Epidemiology and Public Health, Miller School of Medicine, University of Miami, Miami, FL, USA. 5. Department of Neurology, Epidemiology and Public Health, Miller School of Medicine, University of Miami, Miami, FL, USA; Evelyn F. McKnight Brain Institute, University of Miami, Miami, FL, USA. 6. National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA. 7. John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA; Department of Neurology, Epidemiology and Public Health, Miller School of Medicine, University of Miami, Miami, FL, USA; Evelyn F. McKnight Brain Institute, University of Miami, Miami, FL, USA. 8. Department of Neurology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
Abstract
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has been associated with greater cerebral white matter hyperintensity (WMH) volume and microbleeds. The adiponutrin (PNPLA3) rs738409 G variant, a robust NAFLD susceptibility variant, has been variably associated with carotid atherosclerosis. We hypothesized that this variant is associated with WMH volume, microbleeds, covert brain infarction (CBI), and small perivascular spaces. METHODS: We performed a cross-sectional analysis of the Northern Manhattan Study-MRI Substudy. The associations between the rs738409 G variant allele and outcomes were assessed using linear regression for WMH volume, logistic regression for microbleeds and CBI, and Poisson regression for small perivascular spaces. Models were adjusted for age, sex, principal components, diabetes, and body mass index. RESULTS: We included 1063 Northern Manhattan Study participants who had brain MRI and genotype data available (mean age 70 ± 9 years, 61% women). The G allele frequency was 24%. The prevalence of any microbleeds and CBI were 8% and 18%, respectively. The median WMH volume and small perivascular space count score were 7.7 mL and 6, respectively. GG homozygosity, but not heterozygosity, was associated with WMH volume (β = 0.27; 95% CI, 0.03, 0.51) compared to non-carriers. Having at least one G allele was associated with the presence of microbleeds (Odds ratio, 1.78; 95% CI, 1.02, 3.12); the association was attenuated in other models. No associations were observed for CBI and small perivascular spaces. CONCLUSION: The PNPLA3 rs738409 G allele was associated with greater WMH volume, and inconsistent associations with microbleeds were seen.
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) has been associated with greater cerebral white matter hyperintensity (WMH) volume and microbleeds. The adiponutrin (PNPLA3) rs738409 G variant, a robust NAFLD susceptibility variant, has been variably associated with carotid atherosclerosis. We hypothesized that this variant is associated with WMH volume, microbleeds, covert brain infarction (CBI), and small perivascular spaces. METHODS: We performed a cross-sectional analysis of the Northern Manhattan Study-MRI Substudy. The associations between the rs738409 G variant allele and outcomes were assessed using linear regression for WMH volume, logistic regression for microbleeds and CBI, and Poisson regression for small perivascular spaces. Models were adjusted for age, sex, principal components, diabetes, and body mass index. RESULTS: We included 1063 Northern Manhattan Study participants who had brain MRI and genotype data available (mean age 70 ± 9 years, 61% women). The G allele frequency was 24%. The prevalence of any microbleeds and CBI were 8% and 18%, respectively. The median WMH volume and small perivascular space count score were 7.7 mL and 6, respectively. GG homozygosity, but not heterozygosity, was associated with WMH volume (β = 0.27; 95% CI, 0.03, 0.51) compared to non-carriers. Having at least one G allele was associated with the presence of microbleeds (Odds ratio, 1.78; 95% CI, 1.02, 3.12); the association was attenuated in other models. No associations were observed for CBI and small perivascular spaces. CONCLUSION: The PNPLA3 rs738409 G allele was associated with greater WMH volume, and inconsistent associations with microbleeds were seen.
Authors: J Gutierrez; M S V Elkind; C Dong; M Di Tullio; T Rundek; R L Sacco; C B Wright Journal: AJNR Am J Neuroradiol Date: 2017-03-24 Impact factor: 3.825
Authors: Bo Kobberø Lauridsen; Stefan Stender; Thomas Skårup Kristensen; Klaus Fuglsang Kofoed; Lars Køber; Børge G Nordestgaard; Anne Tybjærg-Hansen Journal: Eur Heart J Date: 2018-02-01 Impact factor: 29.983
Authors: Alessia Di Costanzo; Laura D'Erasmo; Licia Polimeni; Francesco Baratta; Paola Coletta; Michele Di Martino; Lorenzo Loffredo; Ludovica Perri; Fabrizio Ceci; Anna Montali; Gabriella Girelli; Bruna De Masi; Antonio Angeloni; Carlo Catalano; Marianna Maranghi; Maria Del Ben; Francesco Angelico; Marcello Arca Journal: Atherosclerosis Date: 2016-12-21 Impact factor: 5.162
Authors: Rosalinda Posadas-Sánchez; Ángel René López-Uribe; Carlos Posadas-Romero; Nonanzit Pérez-Hernández; José Manuel Rodríguez-Pérez; Wendy Angélica Ocampo-Arcos; José Manuel Fragoso; Guillermo Cardoso-Saldaña; Gilberto Vargas-Alarcón Journal: Immunobiology Date: 2016-09-03 Impact factor: 3.144
Authors: Michelle R Caunca; Victor Del Brutto; Hannah Gardener; Nirav Shah; Nelly Dequatre-Ponchelle; Ying Kuen Cheung; Mitchell S V Elkind; Truman R Brown; Charlotte Cordonnier; Ralph L Sacco; Clinton B Wright Journal: J Am Heart Assoc Date: 2016-09-16 Impact factor: 5.501
Authors: Stefan Stender; Julia Kozlitina; Børge G Nordestgaard; Anne Tybjærg-Hansen; Helen H Hobbs; Jonathan C Cohen Journal: Nat Genet Date: 2017-04-24 Impact factor: 38.330