PNPLA3 association with alcoholic liver disease in a cohort of heavy drinkers

Bhanu Prakash Kolla, Terry D. Schneekloth, Joanna M Biernacka, Vijay Shah, Konstantinos N Lazaridis, Jennifer Geske, Victor M Karpyak

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Aims: Prior studies have established variation at the PNPLA3 gene to be associated with a risk of developing alcoholic liver disease (ALD). We attempt to replicate this finding and other potential genetic variations previously associated with ALD utilizing a case-control design in a cohort of subjects with alcohol use disorders. Short summary: This case-control study performed in a US clinical sample of heavy drinkers, replicates the previously reported association between ALD and rs738409 polymorphism in the PNPLA3 gene in heavy drinkers. This association persisted after accounting for the subject's diabetes status. Methods: Patients of European ancestry with a history of ALD were identified (n = 169). Controls consisted of patients without ALD who were from the same cohorts and were ≥ 30 years of age, had lifetime total years drinking ≥20 and lifetime maximum drinks per day ≥12 (n = 259). Patients were genotyped for 40 candidate single nucleotide polymorphisms (SNPs) selected for the purpose of testing their association with ALD. The association of each SNP with ALD was tested using a logistic regression model, assuming log-additive allele effects. Bonferroni correction was applied and multivariable logistic regression models were used to account for relevant covariates. Results: Age, sex, and body mass index (BMI) distributions were similar between cases and controls. Diabetes was more prevalent in the ALD cases. Three SNPs were associated with ALD at the nominal significance level (rs738409 in PNPLA3, P = 0.00029; rs3741559 in AQP2, P = 0.0185; rs4290029 in NVL, P = 0.0192); only PNPLA3 rs738409 SNP was significant at the Bonferroni-corrected P-value threshold of 0.00125. Association results remained significant after adjustment for diabetes status. Conclusion: Our case-control study confirmed that PNPLA3 rs738409 SNP is associated with ALD. This is an important replication in a US clinical sample with control subjects who had long histories of alcohol consumption.

Original languageEnglish (US)
Pages (from-to)357-360
Number of pages4
JournalAlcohol and Alcoholism
Volume53
Issue number4
DOIs
StatePublished - Jan 1 2018

Fingerprint

Alcoholic Liver Diseases
Liver
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Medical problems
Logistic Models
Logistics
Case-Control Studies
Genes
Alcohols
Alcohol Drinking
Drinking
Body Mass Index
Alleles

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology
  • Psychiatry and Mental health

Cite this

PNPLA3 association with alcoholic liver disease in a cohort of heavy drinkers. / Kolla, Bhanu Prakash; Schneekloth, Terry D.; Biernacka, Joanna M; Shah, Vijay; Lazaridis, Konstantinos N; Geske, Jennifer; Karpyak, Victor M.

In: Alcohol and Alcoholism, Vol. 53, No. 4, 01.01.2018, p. 357-360.

Research output: Contribution to journalArticle

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abstract = "Aims: Prior studies have established variation at the PNPLA3 gene to be associated with a risk of developing alcoholic liver disease (ALD). We attempt to replicate this finding and other potential genetic variations previously associated with ALD utilizing a case-control design in a cohort of subjects with alcohol use disorders. Short summary: This case-control study performed in a US clinical sample of heavy drinkers, replicates the previously reported association between ALD and rs738409 polymorphism in the PNPLA3 gene in heavy drinkers. This association persisted after accounting for the subject's diabetes status. Methods: Patients of European ancestry with a history of ALD were identified (n = 169). Controls consisted of patients without ALD who were from the same cohorts and were ≥ 30 years of age, had lifetime total years drinking ≥20 and lifetime maximum drinks per day ≥12 (n = 259). Patients were genotyped for 40 candidate single nucleotide polymorphisms (SNPs) selected for the purpose of testing their association with ALD. The association of each SNP with ALD was tested using a logistic regression model, assuming log-additive allele effects. Bonferroni correction was applied and multivariable logistic regression models were used to account for relevant covariates. Results: Age, sex, and body mass index (BMI) distributions were similar between cases and controls. Diabetes was more prevalent in the ALD cases. Three SNPs were associated with ALD at the nominal significance level (rs738409 in PNPLA3, P = 0.00029; rs3741559 in AQP2, P = 0.0185; rs4290029 in NVL, P = 0.0192); only PNPLA3 rs738409 SNP was significant at the Bonferroni-corrected P-value threshold of 0.00125. Association results remained significant after adjustment for diabetes status. Conclusion: Our case-control study confirmed that PNPLA3 rs738409 SNP is associated with ALD. This is an important replication in a US clinical sample with control subjects who had long histories of alcohol consumption.",
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AU - Schneekloth, Terry D.

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AU - Shah, Vijay

AU - Lazaridis, Konstantinos N

AU - Geske, Jennifer

AU - Karpyak, Victor M

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