Genome-Wide Association Study Identifies Variants Associated With Histologic Features of Nonalcoholic Fatty Liver Disease

Chalasani, Naga; Guo, Xiuqing; Loomba, Rohit; Goodarzi, Mark O.; Haritunians, Talin; Kwon, Soonil; Cui, Jinrui; Taylor, Kent D.; Wilson, Laura; Cummings, Oscar W.; Chen, Yii Der Ida; Rotter, Jerome I.

doi:10.1053/j.gastro.2010.07.057

Cited by 291 publications

(246 citation statements)

References 43 publications

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“…Recently several genetic factors such as patatin-like phospholipase 3 or apolipoprotein C3 have been characterized in NAFLD (Valenti et al, 2010;Petersen et al, 2010). Even genomewide association studies (GWASs) of liver histology in patients with non alcoholic fatty liver disease have been performed to estimate genetic susceptibility to NASH (Chalasani et al, 2010). However, these findings have to be validated.…”

Section: Genetic Prevalencementioning

confidence: 99%

Histopathological Diagnosis of Non-Alcoholic and Alcoholic Fatty Liver Disease

Tannapfel¹,

Flott-Rahmel²

2011

Liver Biopsy in Modern Medicine

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Section: Genetic Prevalencementioning

confidence: 99%

Histopathological Diagnosis of Non-Alcoholic and Alcoholic Fatty Liver Disease

Tannapfel¹,

Flott-Rahmel²

2011

Liver Biopsy in Modern Medicine

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“…Although the K45R substitution was apparently not detrimental to the protein, rs11549147 was suggested to be involved in aberrant exon splicing. Chalasani et al 26 studied the association of histological features of nonalcoholic fatty liver disease with SNPs related to lipid metabolism. They found that the nonalcoholic fatty acid disease score was significantly related to rs2645424 of FDFT1, located in intron 7.…”

Section: Discussionmentioning

confidence: 99%

Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer

Fukuma

Matsui

Koike

et al. 2012

Prostate Cancer Prostatic Dis

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BACKGROUND:We previously conducted a genome-wide linkage analysis of Japanese nuclear families affected with prostate cancer and showed that the susceptibility to prostate cancer was closely linked to D8S550 at 8p23. The role of farnesyl diphosphate farnesyltransferase (FDFT1), which is located under the peak marker D8S550 at 8p23, and squalene synthase, the enzyme encoded by FDFT1, in prostate cancer was studied. METHODS: The association among common variants of FDFT1 with prostate cancer risk, the promoter activities of FDFT1 with different genotypes and the effects of inhibition of squalene synthase were studied, and the FDFT1 transcript levels of human prostate samples were quantified. RESULTS: The A allele of rs2645429 was significantly associated with prostate cancer risk in a Japanese familial prostate cancer population. Rs2645429 was located in the promoter region of FDFT1, and the AA genotype showed significantly increased promoter activity. The knockdown of FDFT1 mRNA expression or squalene synthase inhibition led to a significant decrease in prostate cancer cell proliferation. Additionally, human prostate cancer specimens expressed significantly higher levels of FDFT1 mRNA compared with noncancerous specimens. Finally, aggressive cancers showed higher transcript levels. CONCLUSIONS: FDFT1 and its encoded enzyme, squalene synthase, may play an important role in prostate cancer development and its aggressive phenotypes.

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“…While studying environment and nutritional behavior remains challenging, the genetic role of the variants located on the genes PNPLA3 (22)(23)(24) and transmembrane 6 superfamily member 2 (TM6SF2) (25) has been shown to modify the risks of hepatic steatosis and fibrosis. In addition, GWAS has identified other genetic variants associated with features of hepatic histology in patients with NAFLD (26). In addition, serum miRNA expression has been shown to correlate with liver steatosis in a twin study with a heritable trait (27) and could also account for familial cirrhosis.…”

Section: Discussionmentioning

confidence: 99%