Association between PNPLA3 rs738409 G variant and MRI cerebrovascular disease biomarkers

JOURNAL OF THE NEUROLOGICAL SCIENCES

卷:416

Article

Parikh, Neal S.¹  Dueker, Nicole²  Varela, Dalila¹  Del Brutto, Victor J.³  Rundek, Tatjana^3,4  Wright, Clinton B.⁵  Sacco, Ralph L.^2,3,4  Elkind, Mitchell S. V.^1,6  Gutierrez, Jose¹ 

[1] Columbia Univ, Dept Neurol, Vagelos Coll Phys & Surg, New York, NY USA

[2] Univ Miami, John P Hussman Inst Human Genom, Miami, FL USA

[3] Univ Miami, Miller Sch Med, Dept Neurol Epidemiol & Publ Hlth, Miami, FL 33136 USA

[4] Univ Miami, Evelyn F McKnight Brain Inst, Miami, FL USA

[5] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA

[6] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA

关键词: Cerebrovascular disease/stroke;    Epidemiology;    Association studies in genetics;    Metabolic disease;    Nonalcoholic fatty liver disease;   

DOI  :  10.1016/j.jns.2020.116981

来源: Elsevier

【 摘 要 】

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 (beta = 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.

【 授权许可】

Free