Dataset Information

Association between PNPLA3 rs738409 G variant and MRI cerebrovascular disease biomarkers.

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.

SUBMITTER: Parikh NS

PROVIDER: S-EPMC9004230 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Publications

Association between PNPLA3 rs738409 G variant and MRI cerebrovascular disease biomarkers.

Parikh Neal S NS Dueker Nicole N Varela Dalila D Del Brutto Victor J VJ Rundek Tatjana T Wright Clinton B CB Sacco Ralph L RL Elkind Mitchell S V MSV Gutierrez Jose J

Journal of the neurological sciences 20200620

<h4>Introduction</h4>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.<h4>Methods</h4>We performed a cross-sectional analysis ...[more]

PMID: 32592869

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Project description:BACKGROUND: In a genome-wide association scan, the single-nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat content. We investigated whether this SNP is associated with the occurrence and progression of nonalcoholic fatty liver disease (NAFLD) in the Japanese population. METHODS: SNP rs738409 was genotyped by the Taqman assay in 253 patients with NAFLD (189 with nonalcoholic steatohepatitis [NASH] and 64 with simple steatosis) and 578 control subjects. All patients with NAFLD underwent liver biopsy. Control subjects had no metabolic disorders. For a case-control study, the ?(2)-test (additive model) was performed. Odds ratios (ORs) were adjusted for age, gender, and body mass index (BMI) by using multiple logistic regression analysis with genotypes (additive model), age, gender, and BMI as the independent variables. Multiple linear regression analysis was performed to test the independent effect of risk allele on clinical parameters while considering the effects of other variables (age, gender, and BMI), which were assumed to be independent of the effect of the SNP. RESULTS: The risk allele (G-allele) frequency of rs738409 was 0.44 in the control subjects and 0.60 in patients with NAFLD; this shows a strong association with NAFLD (additive model, P = 9.4 x 10(-10)). The OR (95% confidence interval) adjusted for age, gender, and BMI was 1.73 (1.25-2.38). Multiple linear regression analysis indicated that the G-allele of rs738409 was significantly associated with increases in aspartate transaminase (AST) (P = 0.00013), alanine transaminase (ALT) (P = 9.1 x 10(-6)), and ferritin levels (P = 0.014), and the fibrosis stage (P = 0.011) in the patients with NAFLD, even after adjustment for age, gender, and BMI. The steatosis grade was not associated with rs738409. CONCLUSIONS: We found that in the Japanese population, individuals harboring the G-allele of rs738409 were susceptible to NAFLD, and that rs738409 was associated with plasma levels of ALT, AST, and ferritin, and the histological fibrosis stage. Our study suggests that PNPLA3 may be involved in the progression of fibrosis in NAFLD.

Project description:BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease worldwide. Current studies have shown that PNPLA3 (Patatin-like phospholipase domain containing 3) rs738409 G/C gene polymorphism is associated with adult nonalcoholic fatty liver disease [1, 2].But there is no consensus on the relationship between PNPLA3 rs738409 G/C gene polymorphism and children NAFLD due to differences in population samples. To this end, a meta-analysis of published research is conducted to comprehensively assess the relationship between PNPLA3 gene polymorphism and NAFLD in children. METHODS:We searched MEDLINE, PubMed, EMBASE, and CENTRAL databases from inception to May 2019. Case-control studies assessing the relationship between PNPLA3 rs738409 G/C gene polymorphism with non-alcoholic fatty liver disease in children were selected according to inclusion and exclusion criteria. Random effects model was used to quantify the association between the PNPLA3 rs738409 G/C gene polymorphism and the susceptibility of children's NAFLD. Fixed effects model was used to quantify the relationship between the PNPLA3 rs738409 G/C gene polymorphism and the severity of NAFLD in children. The Stata 12.0 software was employed for data analysis. RESULTS:A total of nine case-control studies were included in this meta-analysis containing data of 1173 children with NAFLD and 1792 healthy controls. Five studies compared NAFLD children and non-NAFLD healthy populations. Statistical analysis showed that PNPLA3 gene polymorphism was significantly associated with children's NAFLD in the allele contrast, dominant, recessive and over dominant models (G vs C,OR = 3.343, 95% CI = 1.524-7.334; GG + GC vs CC,OR = 3.157, 95% CI = 1.446-6.892;GG vs GC + CC,OR = 5.692, 95% CI = 1.941-16.689; GG + CC vs GC,OR = 2.756, 95% CI = 1.729-4.392). Four case-control studies compared Children with nonalcoholic fatty liver (NAFL) and children with nonalcoholic steatohepatitis (NASH). The results showed that the PNPLA3 gene polymorphism was also significantly associated with the severity of NAFLD in children in recessive gene model (GG vs GC + CC,OR = 14.43, 95% CI = 5.985-34.997); The Egger's test revealed no significant publication bias. CONCLUSIONS:Meta-analysis showed that PNPLA3 gene polymorphism was significantly associated with susceptibility and severity of NAFLD in children.

Dataset Information

Association between PNPLA3 rs738409 G variant and MRI cerebrovascular disease biomarkers.

Introduction

Methods

Results

Conclusion

Publications

Association between PNPLA3 rs738409 G variant and MRI cerebrovascular disease biomarkers.

Similar Datasets

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