A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease
The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological fe...
| Auteurs principaux: | , , , , , , |
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| Format: | Article |
| Langue: | English |
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Springer
2012
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| Accès en ligne: | http://eprints.um.edu.my/5032/1/Zain-2012-A_multi-ethnic_study.pdf |
| _version_ | 1825719028695433216 |
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| author | Zain, Shamsul Mohd Mohamed, Rosmawati Mahadeva, Sanjiv Cheah, Phaik Leng Rampal, Sanjay Basu, Roma Choudhury Mohamed, Zahurin |
| author_facet | Zain, Shamsul Mohd Mohamed, Rosmawati Mahadeva, Sanjiv Cheah, Phaik Leng Rampal, Sanjay Basu, Roma Choudhury Mohamed, Zahurin |
| author_sort | Zain, Shamsul Mohd |
| collection | UM |
| description | The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95 CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95 CI 1.12-3.37, p = 0.018; OR 3.51, 95 CI 1.69-7.26, p = 0.001 and OR 2.05, 95 CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95 CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95 CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95 CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurence of fibrosis in patients with NAFLD. © 2012 The Author(s). |
| first_indexed | 2024-03-06T05:13:24Z |
| format | Article |
| id | um.eprints-5032 |
| institution | Universiti Malaya |
| language | English |
| last_indexed | 2024-03-06T05:13:24Z |
| publishDate | 2012 |
| publisher | Springer |
| record_format | dspace |
| spelling | um.eprints-50322021-02-08T07:53:03Z http://eprints.um.edu.my/5032/ A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease Zain, Shamsul Mohd Mohamed, Rosmawati Mahadeva, Sanjiv Cheah, Phaik Leng Rampal, Sanjay Basu, Roma Choudhury Mohamed, Zahurin R Medicine The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95 CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95 CI 1.12-3.37, p = 0.018; OR 3.51, 95 CI 1.69-7.26, p = 0.001 and OR 2.05, 95 CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95 CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95 CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95 CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurence of fibrosis in patients with NAFLD. © 2012 The Author(s). Springer 2012 Article PeerReviewed application/pdf en http://eprints.um.edu.my/5032/1/Zain-2012-A_multi-ethnic_study.pdf Zain, Shamsul Mohd and Mohamed, Rosmawati and Mahadeva, Sanjiv and Cheah, Phaik Leng and Rampal, Sanjay and Basu, Roma Choudhury and Mohamed, Zahurin (2012) A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease. Human Genetics, 131 (7). pp. 1145-1152. ISSN 0340-6717, DOI https://doi.org/10.1007/s00439-012-1141-y <https://doi.org/10.1007/s00439-012-1141-y>. https://doi.org/10.1007/s00439-012-1141-y doi:10.1007/s00439-012-1141-y |
| spellingShingle | R Medicine Zain, Shamsul Mohd Mohamed, Rosmawati Mahadeva, Sanjiv Cheah, Phaik Leng Rampal, Sanjay Basu, Roma Choudhury Mohamed, Zahurin A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease |
| title | A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease |
| title_full | A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease |
| title_fullStr | A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease |
| title_full_unstemmed | A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease |
| title_short | A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease |
| title_sort | multi ethnic study of a pnpla3 gene variant and its association with disease severity in non alcoholic fatty liver disease |
| topic | R Medicine |
| url | http://eprints.um.edu.my/5032/1/Zain-2012-A_multi-ethnic_study.pdf |
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