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PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity.
J Nutr. 2015 Aug; 145(8):1687-91.JN

Abstract

BACKGROUND

Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity.

OBJECTIVE

The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele.

METHODS

PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m(2)) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and α-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC.

RESULTS

The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04).

CONCLUSION

We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.

Authors+Show Affiliations

Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD;Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden;Internal Medicine, Institution of Scientific Inpatient Care (istituto di ricovero e cura a carattere scientifico, IRCCS) Ca'-Granda Polyclinic Hospital, Milan, Italy; Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy;Internal Medicine, Institution of Scientific Inpatient Care (istituto di ricovero e cura a carattere scientifico, IRCCS) Ca'-Granda Polyclinic Hospital, Milan, Italy; Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy;Internal Medicine, Institution of Scientific Inpatient Care (istituto di ricovero e cura a carattere scientifico, IRCCS) Ca'-Granda Polyclinic Hospital, Milan, Italy; Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy;Department of Medical and Surgical Sciences, Clinical Nutrition Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy; and.Internal Medicine, Institution of Scientific Inpatient Care (istituto di ricovero e cura a carattere scientifico, IRCCS) Ca'-Granda Polyclinic Hospital, Milan, Italy; Department of Pathophysiology and Transplantation (DEPT), University of Milan, Milan, Italy;Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, MD;Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; Department of Medical and Surgical Sciences, Clinical Nutrition Unit, University Magna Graecia of Catanzaro, Catanzaro, Italy; and Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden stefano.romeo@wlab.gu.se.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26136587

Citation

Mondul, Alison, et al. "PNPLA3 I148M Variant Influences Circulating Retinol in Adults With Nonalcoholic Fatty Liver Disease or Obesity." The Journal of Nutrition, vol. 145, no. 8, 2015, pp. 1687-91.
Mondul A, Mancina RM, Merlo A, et al. PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity. J Nutr. 2015;145(8):1687-91.
Mondul, A., Mancina, R. M., Merlo, A., Dongiovanni, P., Rametta, R., Montalcini, T., Valenti, L., Albanes, D., & Romeo, S. (2015). PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity. The Journal of Nutrition, 145(8), 1687-91. https://doi.org/10.3945/jn.115.210633
Mondul A, et al. PNPLA3 I148M Variant Influences Circulating Retinol in Adults With Nonalcoholic Fatty Liver Disease or Obesity. J Nutr. 2015;145(8):1687-91. PubMed PMID: 26136587.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PNPLA3 I148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity. AU - Mondul,Alison, AU - Mancina,Rosellina M, AU - Merlo,Andrea, AU - Dongiovanni,Paola, AU - Rametta,Raffaela, AU - Montalcini,Tiziana, AU - Valenti,Luca, AU - Albanes,Demetrius, AU - Romeo,Stefano, Y1 - 2015/07/01/ PY - 2015/01/16/received PY - 2015/06/04/accepted PY - 2015/7/3/entrez PY - 2015/7/3/pubmed PY - 2015/10/28/medline KW - NAFLD KW - PNPLA3 KW - RBP4 KW - obesity KW - retinol SP - 1687 EP - 91 JF - The Journal of nutrition JO - J. Nutr. VL - 145 IS - 8 N2 - BACKGROUND: Retinol is a lipid-soluble essential nutrient that is stored as retinyl esters in lipid droplets of hepatic stellate cells. Patatin-like phospholipase domain-containing 3 (PNPLA3), through its retinyl-palmitate lipase activity, releases retinol from lipid droplets in hepatic stellate cells in vitro and ex vivo. We have shown that the genetic variant I148M (rs738409) reduces the PNPLA3 retinyl-palmitate lipase activity. OBJECTIVE: The aim of the present genetic association study was to test whether overweight/obese carriers of the PNPLA3 148M mutant allele had lower circulating concentrations of retinol than individuals who are homozygous for the 148I allele. METHODS: PNPLA3 I148M (rs738409) was genotyped by Taqman assay in 76 overweight/obese individuals [BMI (kg/m(2)) ≥25; mean ± SD age: 59.7 ± 11.4 y; male gender: 70%] with a histologic diagnosis of nonalcoholic fatty liver disease (NAFLD; namely the Milan NAFLD cohort) and in 413 obese men (BMI ≥30; mean ± SD age: 57.1 ± 4.9 y) from the α-Tocopherol, β-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinol and α-tocopherol were measured by HPLC in both cohorts. β-Carotene concentrations in the ATBC study were measured by using HPLC. RESULTS: The PNPLA3 148M mutant allele was associated with lower fasting circulating concentrations of retinol (β = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3 148M mutant allele was also associated with lower fasting circulating concentrations of retinol in adults with a BMI ≥30 (ATBC study; β = -0.043, P = 0.04). CONCLUSION: We showed for the first time, to our knowledge, that carriers of the PNPLA3 148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations. SN - 1541-6100 UR - https://www.unboundmedicine.com/medline/citation/26136587/PNPLA3_I148M_Variant_Influences_Circulating_Retinol_in_Adults_with_Nonalcoholic_Fatty_Liver_Disease_or_Obesity_ L2 - https://academic.oup.com/jn/article-lookup/doi/10.3945/jn.115.210633 DB - PRIME DP - Unbound Medicine ER -