Development of gene polymorphisms in meditators of nonalcoholic fatty liver disease

Abstract

Abstract. Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, the morbidity of which closely correlates with diversity of ethnicity, minority, family and location. Its histology spans from simple steatosis, to nonalcoholic steatohepatitis, which ultimately results in fibrosis, cirrhosis and hepatocellular carcinoma. The accelerating prevalence of NAFLD is due to an incremental incidence of metabolic syndrome that is distinguished by dyslipidemia, glucose impairment, obesity, excessive oxidative stress and adipocytokine impairment. Additionally, the pathogenesis of NAFLD is thought to be a multifactorial and complicated disease associated with lifestyle habits, nutritional factors and genetics. However, the pathogenesis and underlying mechanism in the development of NAFLD caused by genetics remains unclear. People have been increasingly emphasizing on the relationship between NAFLD and gene polymorphisms in recent years, with the aim of having a comprehensive elucidation of associated gene polymorphisms influencing the pathogenesis of the disease. In the current article, the authors attempted to critically summarize the most recently identified gene polymorphisms from the facets of glucose metabolism, fatty acid metabolism, oxidative stress and related cytokines in NAFLD that contribute to promoting the progression of the disease.

Oxidative Stress in Non-Alcoholic Fatty Liver Disease

“…Excessive CYP2E1 activation in perivenular hepatocytes causes an increase in the area of hepatocyte damage, at least in CYP2E1 transgenic murine models. In particular, the variant CYP4502E1*5B (RsaI, −1053C>T) seems to increase the enzyme transcription and activity, resulting in an increase in the ROS production in alcoholic cirrhotic patients, but evidence is not yet available for NAFLD patients [369].…”

Association of sorting and assembly machinery component 50 homolog gene polymorphisms with nonalcoholic fatty liver disease susceptibility

“…[ 6 ] According to the present data, NAFLD affects 10%–30% of the general population in various countries, which has been viewed as a huge global health burden. [ 7 , 8 ]…”

“…[6] According to the present data, NAFLD affects 10%-30% of the general population in various countries, which has been viewed as a huge global health burden. [7,8] Little is known about the latent mechanism involved in the development and pathogenesis of NAFLD, and yet it is a complicated metabolic process in which both environmental and genetic factors are etiology. [9] At present, genome-wide association studies (GWAS) have demonstrated several conspicuous genetic susceptibility genes such as PNPLA3, SAMM50, PARVB, APOC3, PPAR-γ, NCANCILP2, FABP1, AGTR1, GSTs, which had been verified the crucial roles in the disease onset and progression of NAFLD.…”

Metabolic syndrome and cardiovascular pathology: focus on non-alcoholic fatty liver disease

“…Другая мутация в гене TM6SF2, кодирующем трансмембранный белок 6 суперсемейства-2, способствующая задержке триглицеридов и холестерина в печени, с одной стороны, предрасполагает к НАЖБП и фиброзу печени, с другой -обладает кардиопротективными эффектами за счет снижения уровня секреции ЛПОНП и концентрации триглицеридов в сыворотке крови [41]. Данные ряда исследований свидетельствуют, что мутации генов, кодирующих рецепторы адипонектина и лептина, связаны не только с более тяжелым поражением печени, но и с выраженными метаболическими нарушениями (дислипидемия, сахарный диабет), предрасполагающими к развитию и прогрессированию сердечно-сосудистых заболеваний [42,43].…”