Could inherited predisposition drive non-obese fatty liver disease? Results from German tertiary referral centers.

TY - JOUR

T1 - Could inherited predisposition drive non-obese fatty liver disease? Results from German tertiary referral centers.

AU - Krawczyk, Marcin

AU - Bantel, Heike

AU - Rau, Monika

AU - Schattenberg, Jörn M

AU - Grünhage, Frank

AU - Pathil, Anita

AU - Demir, Münevver

AU - Kluwe, Johannes

AU - Boettler, Tobias

AU - Weber, Susanne N

AU - Geier, Andreas

AU - Lammert, Frank

AU - NAFLD Clinical Study Group (NAFLD CSG)

PY - 2018/5

Y1 - 2018/5

N2 - Non-alcoholic fatty liver disease (NAFLD) is frequent among obese individuals with metabolic syndrome. Variants PNPLA3 p.I148M, TM6SF2 p.E167K and MBOAT7 rs641738 are associated with higher liver fat contents. Here we analyzed 63 biopsied non-obese, non-diabetic patients with NAFLD (39 men, age: 20-72 years) recruited within the German NAFLD CSG program. The frequencies of the PNPLA3, TM6SF2 and MBOAT7 polymorphisms were compared with the remaining patients in the NAFLD CSG cohort and with a control population (n = 174). Serum CK18-M30 was measured by ELISA. In non-obese NAFLD patients, the frequency of the PNPLA3 p.I148M allele (74.6%), but not of the TM6SF2 or MBOAT7 polymorphisms, was significantly (P < 0.05) higher as compared to the other patients in the NAFLD CSG cohort (54.9%) or controls (40.2%). The presence of the minor PNPLA3 p.I148M risk allele increased the risk of developing NAFLD (OR = 3.29, P < 0.001) and was associated with higher steatosis, fibrosis, and serum CK18-M30 levels (all P < 0.05). According to the population attributable fraction (PAF), 49.8% of NAFLD cases could be eliminated if the PNPLA3 mutation was absent. The MBOAT7 polymorphism was more frequent (P = 0.019) in patients with severe hepatic steatosis. In conclusion, PNPLA3, and to a lesser extent, MBOAT7 variants are associated with NAFLD risk and modulate liver injury in non-obese patients without diabetes.

AB - Non-alcoholic fatty liver disease (NAFLD) is frequent among obese individuals with metabolic syndrome. Variants PNPLA3 p.I148M, TM6SF2 p.E167K and MBOAT7 rs641738 are associated with higher liver fat contents. Here we analyzed 63 biopsied non-obese, non-diabetic patients with NAFLD (39 men, age: 20-72 years) recruited within the German NAFLD CSG program. The frequencies of the PNPLA3, TM6SF2 and MBOAT7 polymorphisms were compared with the remaining patients in the NAFLD CSG cohort and with a control population (n = 174). Serum CK18-M30 was measured by ELISA. In non-obese NAFLD patients, the frequency of the PNPLA3 p.I148M allele (74.6%), but not of the TM6SF2 or MBOAT7 polymorphisms, was significantly (P < 0.05) higher as compared to the other patients in the NAFLD CSG cohort (54.9%) or controls (40.2%). The presence of the minor PNPLA3 p.I148M risk allele increased the risk of developing NAFLD (OR = 3.29, P < 0.001) and was associated with higher steatosis, fibrosis, and serum CK18-M30 levels (all P < 0.05). According to the population attributable fraction (PAF), 49.8% of NAFLD cases could be eliminated if the PNPLA3 mutation was absent. The MBOAT7 polymorphism was more frequent (P = 0.019) in patients with severe hepatic steatosis. In conclusion, PNPLA3, and to a lesser extent, MBOAT7 variants are associated with NAFLD risk and modulate liver injury in non-obese patients without diabetes.

KW - Adult

KW - Aged

KW - Alleles

KW - Biomarkers

KW - Biopsy

KW - Female

KW - Genetic Association Studies

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Germany

KW - Humans

KW - Liver Function Tests

KW - Male

KW - Middle Aged

KW - Non-alcoholic Fatty Liver Disease/diagnosis

KW - Risk Factors

KW - Severity of Illness Index

KW - Tertiary Care Centers

KW - Young Adult

U2 - 10.1038/s10038-018-0420-4

DO - 10.1038/s10038-018-0420-4

M3 - SCORING: Journal article

C2 - 29483677

VL - 63

SP - 621

EP - 626

JO - J HUM GENET

JF - J HUM GENET

SN - 1434-5161

IS - 5

ER -