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PNPLA3 mutation increases risk for NAFLD regardless of weight

Researchers in Japan found that Japanese adults who carried a PNPLA3 mutant variation had an increased risk for developing nonalcoholic fatty liver disease and other health problems regardless of whether or not they had a normal weight, according to newly published data.

According to a press release, nearly 20% of all Japanese people carry the mutant gene and are at a higher risk for NAFLD and renal function dysfunction when compared to those without the gene. This suggests that the mutation may be used for early classification of individuals at high risk for NAFLD and decreased renal function no matter their weight.

Kentaro Oniki

“We hope that clarifying the risk factors for NAFLD among normal-weight subjects will help to identify susceptible populations for the early prevention and treatment of NAFLD and its complications,” Kentaro Oniki, PhD, of the Graduate School of Pharmaceutical Sciences at Kumamoto University,  said in a press release. “Especially in Asians.”

Oniki and colleagues performed a cross-sectional study of 740 Japanese adults and a retrospective longitudinal study of 393 adults from a health screening program who had 5 years of medical records that were available. The researchers investigated whether there were any associations between the genotype and the risk of NAFLD or a decline in renal function. These variables were analyzed and compared among overweight and normal-weight participants.

Overall, PNPLA3 polymorphism rs738409 genotype was associated with a risk for NAFLD in normal-weight patients (OR = 3.06; 95% CI, 1.11-8.43; P < .05).

Among the 591 patients included in the cross-sectional study, the risk of NAFLD was higher in the patients with the PNPLA3 C/G or G/G genotypes compared with patients with the C/C genotype (adjusted OR = 2.31; 95% CI, 1.26-4.25 or aOR = 2.83; 95% CI, 1.31-6.11, respectively). Participants with the PNPLA3 G/G genotype and a normal weight had a lower estimated glomerular filtration rate (eGFR) compared with participants with the PNPLA3 C/C genotype (P < .05).

In the longitudinal analysis, the risk for NAFLD was higher in patients with the PNPLA3 C/G or G/G genotypes compared with patients with the C/C genotype (aOR = 2.67; 95% CI, 1.3-5.49 or aOR = 3.09; 95% CI, 1.26-7.58, respectively). In addition, the C/G and G/G genotypes in normal-weight patients also had increased risk (aOR = 4.01; 95% CI, 1.34-12.02 or aOR = 5.47; 95% CI, 1.64-18.23, respectively).

NAFLD prevalence was greater in the participants with normal weight who carried the PNPLA3 G/G gene during the observation period. Among the overweight participants, none of the genotypes were significantly associated in the cross-sectional and longitudinal analyses (P = .58).

The researchers concluded: “The information regarding the PNPLA3 genotype in normal-weight subjects may be utilized for health promotion, although further investigations with a larger number of subjects are needed to verify and further clarify these findings.” – by Melinda Stevens

Disclosures: The study was funded by grants-in-aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology and in part by a grant from the Smoking Research Foundation. Healio.com/Hepatology was unable to confirm relevant financial disclosures at the time of publication.