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PNPLA3 genetic variants determine hepatic steatosis in non-obese chronic hepatitis C patients.

Huang CF, Chen JJ, Yeh ML, Huang CI, Hsieh MY, Yang HL, Dai CY, Huang JF, Lin ZY, Chen SC, Chuang WL, Chen YL, Yu ML - Sci Rep (2015)

Bottom Line: PNPLA3 genetic variants had minimal effects on hepatic steatosis among overweight or obese patients.In conclusions, both PNPLA3 genetic variants and BMI played important roles in hepatic steatosis among Asian chronic hepatitis C patients.However, the genetic effect was mainly restricted to non-obese patients.

View Article: PubMed Central - PubMed

Affiliation: 1] Graguate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan [2] Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan [3] Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan [4] Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

ABSTRACT
The influence of patatin-like phospholipase domain-containing 3 (PNPLA3) genetic variants in the development of liver steatosis in Asian chronic hepatitis C patients remains elusive. A total of 1018 biopsy-proven chronic hepatitis C patients were enrolled for evaluation. The proportions of PNPLA3 rs738409 GG genotype carriage were 7.8% (44/563), 15.8% (58/367) and 19.3% (17/88) in patients with no (liver fat content < 5%), mild (5-33%) and moderate/severe (> 66%) hepatic steatosis, respectively (trend P < 0.001). Stepwise logistic regression analysis revealed that the strongest factor independently associated with steatosis was the carriage of the PNPLA3 rs738409 GG genotype (odds ratio [OR]/95% confidence intervals [CI]:2.34/1.557-3.515, P < 0.001). Among the patients with BMI < 24 kg/m(2), carriage of the rs738409 GG genotype was the only factor associated with hepatic steatosis (OR/CI:3.44/1.824-6.500, P < 0.001). PNPLA3 genetic variants had minimal effects on hepatic steatosis among overweight or obese patients. Compared to patients with BMI < 24 kg/m(2)/non-GG genotype, those with BMI >24 kg/m(2)/GG genotype were more likely to have hepatic steatosis (OR/CI:3.87/2.292-6.524, P < 0.001). In conclusions, both PNPLA3 genetic variants and BMI played important roles in hepatic steatosis among Asian chronic hepatitis C patients. However, the genetic effect was mainly restricted to non-obese patients.

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Percentage of PNPLA3 rs38409 genotype in patients with hepatic steatosis <5%, 5–33% and >33%, respectively.
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f1: Percentage of PNPLA3 rs38409 genotype in patients with hepatic steatosis <5%, 5–33% and >33%, respectively.

Mentions: Because BMI and PNPLA3 genetic variants are both important determinants of hepatic steatosis, we further explored the influence of the PNPLA3 SNP in steatosis among patients with different BMIs. Patients were categorized into normal or underweight (<24 kg/m2), overweight (24–27 kg/m2) or obese (>27 kg/m2) according to the definition of the Health Promotion Administration of the Ministry of Health and Welfare in Taiwan19. Among the patients with normal body weights, hepatic steatosis was associated with a higher r-GT level, a lower proportion of HBsAg seropositivity and a higher proportion of PNPLA3 rs738409 G genotype carriage in univariate analysis (Table 3). In multivariateanalysis, carriage of the rs738409 GG genotype was the only factor associated with hepatic steatosis (OR/CI:3.44/1.824–6.500, P < 0.001) by using the recessive model, whereas factors associated with steatosis were the rs738409 GG/GC genotype (OR/CI:1.69/1.101–2.614, P = 0.02) and HBV dual infection (OR/CI: 0.42/0.188–0.940, P = 0.04) using the dominant model (Table 4). Among the overweight patients (BMIbetween 24–27 kg/m2), the univariate analysis revealed that the patients with steatosis were older and were more likely to have diabetes, lower platelet counts and a higher r-GT level; while the steatotic patients had a substantially higher proportion of rs738409 GG genotype carriage, the difference was not significant (P=0.06) (Table 3). Multivariate analysis revealed that the factors associated with steatosis in overweight CHC patients included age (OR/CI:1.023/1.001–1.045, P = 0.04) and diabetes (OR/CI:2.201/1.055–3.875, P = 0.03), but not PNPLA3 rs738409 genotype variants (Table 4). For obese patients, hepatic steatosis was only associated with a higher r-GT level in the univariate analysis (Table 3), although no factors were associated with hepatic steatosis in obese CHC patients in the multivariate analysis. The impact of the PNPLA3 rs738409 genotype on fatty liver varied among patients with different BMIs (Supplementary Fig 1). We further explored the role of the SNP in patients with different degrees of hepatic steatosis. The proportion of PNPLA3 rs738409 GG genotype carriage was 7.8% (44/563), 15.8% (58/367) and 19.3% (17/88) in patients with no, mild, and moderate/severe hepatic steatosis, respectively (trend P < 0.001) (fig. 1).


PNPLA3 genetic variants determine hepatic steatosis in non-obese chronic hepatitis C patients.

Huang CF, Chen JJ, Yeh ML, Huang CI, Hsieh MY, Yang HL, Dai CY, Huang JF, Lin ZY, Chen SC, Chuang WL, Chen YL, Yu ML - Sci Rep (2015)

Percentage of PNPLA3 rs38409 genotype in patients with hepatic steatosis <5%, 5–33% and >33%, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490397&req=5

f1: Percentage of PNPLA3 rs38409 genotype in patients with hepatic steatosis <5%, 5–33% and >33%, respectively.
Mentions: Because BMI and PNPLA3 genetic variants are both important determinants of hepatic steatosis, we further explored the influence of the PNPLA3 SNP in steatosis among patients with different BMIs. Patients were categorized into normal or underweight (<24 kg/m2), overweight (24–27 kg/m2) or obese (>27 kg/m2) according to the definition of the Health Promotion Administration of the Ministry of Health and Welfare in Taiwan19. Among the patients with normal body weights, hepatic steatosis was associated with a higher r-GT level, a lower proportion of HBsAg seropositivity and a higher proportion of PNPLA3 rs738409 G genotype carriage in univariate analysis (Table 3). In multivariateanalysis, carriage of the rs738409 GG genotype was the only factor associated with hepatic steatosis (OR/CI:3.44/1.824–6.500, P < 0.001) by using the recessive model, whereas factors associated with steatosis were the rs738409 GG/GC genotype (OR/CI:1.69/1.101–2.614, P = 0.02) and HBV dual infection (OR/CI: 0.42/0.188–0.940, P = 0.04) using the dominant model (Table 4). Among the overweight patients (BMIbetween 24–27 kg/m2), the univariate analysis revealed that the patients with steatosis were older and were more likely to have diabetes, lower platelet counts and a higher r-GT level; while the steatotic patients had a substantially higher proportion of rs738409 GG genotype carriage, the difference was not significant (P=0.06) (Table 3). Multivariate analysis revealed that the factors associated with steatosis in overweight CHC patients included age (OR/CI:1.023/1.001–1.045, P = 0.04) and diabetes (OR/CI:2.201/1.055–3.875, P = 0.03), but not PNPLA3 rs738409 genotype variants (Table 4). For obese patients, hepatic steatosis was only associated with a higher r-GT level in the univariate analysis (Table 3), although no factors were associated with hepatic steatosis in obese CHC patients in the multivariate analysis. The impact of the PNPLA3 rs738409 genotype on fatty liver varied among patients with different BMIs (Supplementary Fig 1). We further explored the role of the SNP in patients with different degrees of hepatic steatosis. The proportion of PNPLA3 rs738409 GG genotype carriage was 7.8% (44/563), 15.8% (58/367) and 19.3% (17/88) in patients with no, mild, and moderate/severe hepatic steatosis, respectively (trend P < 0.001) (fig. 1).

Bottom Line: PNPLA3 genetic variants had minimal effects on hepatic steatosis among overweight or obese patients.In conclusions, both PNPLA3 genetic variants and BMI played important roles in hepatic steatosis among Asian chronic hepatitis C patients.However, the genetic effect was mainly restricted to non-obese patients.

View Article: PubMed Central - PubMed

Affiliation: 1] Graguate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan [2] Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan [3] Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan [4] Faculty of Internal Medicine, School of Medicine, College of Medicine, and Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

ABSTRACT
The influence of patatin-like phospholipase domain-containing 3 (PNPLA3) genetic variants in the development of liver steatosis in Asian chronic hepatitis C patients remains elusive. A total of 1018 biopsy-proven chronic hepatitis C patients were enrolled for evaluation. The proportions of PNPLA3 rs738409 GG genotype carriage were 7.8% (44/563), 15.8% (58/367) and 19.3% (17/88) in patients with no (liver fat content < 5%), mild (5-33%) and moderate/severe (> 66%) hepatic steatosis, respectively (trend P < 0.001). Stepwise logistic regression analysis revealed that the strongest factor independently associated with steatosis was the carriage of the PNPLA3 rs738409 GG genotype (odds ratio [OR]/95% confidence intervals [CI]:2.34/1.557-3.515, P < 0.001). Among the patients with BMI < 24 kg/m(2), carriage of the rs738409 GG genotype was the only factor associated with hepatic steatosis (OR/CI:3.44/1.824-6.500, P < 0.001). PNPLA3 genetic variants had minimal effects on hepatic steatosis among overweight or obese patients. Compared to patients with BMI < 24 kg/m(2)/non-GG genotype, those with BMI >24 kg/m(2)/GG genotype were more likely to have hepatic steatosis (OR/CI:3.87/2.292-6.524, P < 0.001). In conclusions, both PNPLA3 genetic variants and BMI played important roles in hepatic steatosis among Asian chronic hepatitis C patients. However, the genetic effect was mainly restricted to non-obese patients.

No MeSH data available.


Related in: MedlinePlus