PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease.
PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease.
Background and Aims: Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3 (
PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by
PNPLA3 rs738409 polymorphism.
Methods: The variant of
PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed NAFLD. Visceral fat area (VFA) was measured by bioelectrical impedance. Significant liver fibrosis (SF), defined as stage F ≥2 on histology, was the outcome measure of interest.
Results: The distribution of
PNPLA3 genotypes was CC: 27.5%, CG: 48.2%, and GG: 24.3%. Higher VFA was associated with greater risk of having SF (adjusted-odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02-1.04,
p<0.05), independent of potential confounders. Among subjects with the same VFA level, the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not. Stratified analysis showed that
PNPLA3 rs738409 significantly influenced the association between VFA and SF. VFA remained significantly associated with SF only among the rs738409 G-allele carriers (adjusted-OR: 1.05; 95% CI: 1.03-1.08 for the GG group; and adjusted-OR:1.03; 95% CI: 1.01-1.04 for the GC group). There was a significant interaction between VFA and
PNPLA3 rs738409 genotype (P
interaction
=0.004).
Conclusions:
PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult individuals with biopsy-proven NAFLD. Existence of the
PNPLA3 rs738409 G allele and VFA interact to increase risk of SF.
Metabolic dysfunction-associated fatty liver disease, Nonalcoholic fatty liver disease, Significant fibrosis, Single nucleotide polymorphism, Visceral fat area
439-448
Li, Gang
3db754ee-6c8c-4db8-b439-11c3416c0c39
Tang, Liang-Jie
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Zhu, Pei-Wu
499c3a3b-0b72-4eef-9a21-265dfb13f1a3
Huang, Ou-Yang
4e0d1e1a-912f-4a3e-a11e-bac143fc53cf
Rios, Rafael S.
87af9c23-e8ec-4fc0-9e89-2acf344b39eb
Zheng, Kenneth I.
267ffebb-7dd6-47a6-a712-cfd3079db91b
Chen, Sui-Dan
79f12994-ebe6-4b19-ab44-71fe6c3f1e07
Ma, Hong-Lei
607fe477-0dfd-408f-a8f0-29a545dedf35
Targher, Giovanni
bf107883-c7ea-434d-b8e3-633fe95e0d18
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Pan, Xiao-Yan
06913e8c-5bef-45db-93ae-9afbbc3b9e00
Zheng, Ming-Hua
2b327718-8803-4615-b04f-028b2269b2de
22 October 2021
Li, Gang
3db754ee-6c8c-4db8-b439-11c3416c0c39
Tang, Liang-Jie
4f58a8b1-4bb2-4e80-9670-b41220b47837
Zhu, Pei-Wu
499c3a3b-0b72-4eef-9a21-265dfb13f1a3
Huang, Ou-Yang
4e0d1e1a-912f-4a3e-a11e-bac143fc53cf
Rios, Rafael S.
87af9c23-e8ec-4fc0-9e89-2acf344b39eb
Zheng, Kenneth I.
267ffebb-7dd6-47a6-a712-cfd3079db91b
Chen, Sui-Dan
79f12994-ebe6-4b19-ab44-71fe6c3f1e07
Ma, Hong-Lei
607fe477-0dfd-408f-a8f0-29a545dedf35
Targher, Giovanni
bf107883-c7ea-434d-b8e3-633fe95e0d18
Byrne, Christopher
1370b997-cead-4229-83a7-53301ed2a43c
Pan, Xiao-Yan
06913e8c-5bef-45db-93ae-9afbbc3b9e00
Zheng, Ming-Hua
2b327718-8803-4615-b04f-028b2269b2de
Li, Gang, Tang, Liang-Jie, Zhu, Pei-Wu, Huang, Ou-Yang, Rios, Rafael S., Zheng, Kenneth I., Chen, Sui-Dan, Ma, Hong-Lei, Targher, Giovanni, Byrne, Christopher, Pan, Xiao-Yan and Zheng, Ming-Hua
(2021)
PNPLA3 rs738409 C>G Variant Influences the Association Between Visceral Fat and Significant Fibrosis in Biopsy-proven Nonalcoholic Fatty Liver Disease.
Journal of Clinical and Translational Hepatology, 10 (3), .
(doi:10.14218/JCTH.2021.00286).
Abstract
Background and Aims: Intra-abdominal visceral fat accumulation and patatin-like phospholipase domain containing 3 (
PNPLA3) rs738409 G/C gene polymorphism confer a greater susceptibility to nonalcoholic fatty liver disease (NAFLD). We examined whether the relationship between visceral fat accumulation and liver disease severity may be influenced by
PNPLA3 rs738409 polymorphism.
Methods: The variant of
PNPLA3 rs738409 was genotyped within 523 Han individuals with biopsy-confirmed NAFLD. Visceral fat area (VFA) was measured by bioelectrical impedance. Significant liver fibrosis (SF), defined as stage F ≥2 on histology, was the outcome measure of interest.
Results: The distribution of
PNPLA3 genotypes was CC: 27.5%, CG: 48.2%, and GG: 24.3%. Higher VFA was associated with greater risk of having SF (adjusted-odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.02-1.04,
p<0.05), independent of potential confounders. Among subjects with the same VFA level, the risk of SF was greater among carriers of the rs738409 G genotype than among those who did not. Stratified analysis showed that
PNPLA3 rs738409 significantly influenced the association between VFA and SF. VFA remained significantly associated with SF only among the rs738409 G-allele carriers (adjusted-OR: 1.05; 95% CI: 1.03-1.08 for the GG group; and adjusted-OR:1.03; 95% CI: 1.01-1.04 for the GC group). There was a significant interaction between VFA and
PNPLA3 rs738409 genotype (P
interaction
=0.004).
Conclusions:
PNPLA3 rs738409 G allele has a moderate effect on the association between VFA and risk of SF in adult individuals with biopsy-proven NAFLD. Existence of the
PNPLA3 rs738409 G allele and VFA interact to increase risk of SF.
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Accepted/In Press date: 22 September 2021
e-pub ahead of print date: 22 October 2021
Published date: 22 October 2021
Additional Information:
© 2022 Authors.
Keywords:
Metabolic dysfunction-associated fatty liver disease, Nonalcoholic fatty liver disease, Significant fibrosis, Single nucleotide polymorphism, Visceral fat area
Identifiers
Local EPrints ID: 451741
URI: http://eprints.soton.ac.uk/id/eprint/451741
ISSN: 2225-0719
PURE UUID: addc68dc-cf09-4db0-b66e-30ad429f3da0
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Date deposited: 25 Oct 2021 16:30
Last modified: 17 Mar 2024 02:49
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Contributors
Author:
Gang Li
Author:
Liang-Jie Tang
Author:
Pei-Wu Zhu
Author:
Ou-Yang Huang
Author:
Rafael S. Rios
Author:
Kenneth I. Zheng
Author:
Sui-Dan Chen
Author:
Hong-Lei Ma
Author:
Giovanni Targher
Author:
Xiao-Yan Pan
Author:
Ming-Hua Zheng
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