PNPLA3 1148M Variant Influences Circulating Retinol in Adults with Nonalcoholic Fatty Liver Disease or Obesity

• Background: Retinal 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 1148M (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 retinal than individuals who are homozygous for the 1481 allele. Methods: PNPLA31148M (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 alpha-Tocopherol, (beta-Carotene Cancer Prevention (ATBC) Study. Serum concentrations of retinal and alpha-tocopherol were measured by HPLC in both cohorts. beta-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 retinal (beta = -0.289, P = 0.03) in adults with NAFLD (Milan NAFLD cohort). The PNPLA3148M mutant allele was also associated with lower fasting circulating concentrations of retinal in adults with a BMI >= 30 (ATBC study; [beta = -0.043, P = 0.041. Conclusion: We showed for the first time, to our knowledge, that carriers of the PNPLA3148M allele with either fatty liver plus obesity or obesity alone have lower fasting circulating retinol concentrations.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine (hsv//eng)

Nyckelord

PNPLA3

retinal

NAFLD

obesity

RBP4

PROTEIN-CALORIE MALNUTRITION

SERUM VITAMIN-A

BINDING-PROTEIN

HEPATOCELLULAR-CARCINOMA

PREALBUMIN CONCENTRATIONS

I148M POLYMORPHISM

RS738409

ASSOCIATION

METABOLISM

TRANSPORT

Nutrition & Dietetics

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