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      Ethnic differences and heterogeneity in genetic and metabolic makeup contributing to nonalcoholic fatty liver disease

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          Abstract

          Obesity is the most prevalent noncommunicable disease in the 21st century, associated with triglyceride deposition in hepatocytes leading to nonalcoholic fatty liver disease (NAFLD). NAFLD is now present in around a third of the world’s population. Epidemiological studies have concluded that ethnicity plays a role in complications and treatment response. However, definitive correlations of ethnicity with NAFLD are thoroughly under-reported. A comprehensive review was conducted on ethnic variation in NAFLD patients and its potential role as a crucial effector in complications and treatment response. The highest NAFLD prevalence is observed in Hispanic populations, exhibiting a worse disease progression. In contrast, African-Caribbeans exhibit the lowest risk, with less severe steatosis and inflammation, lower levels of triglycerides, and less metabolic derangement, but conversely higher prevalence of insulin resistance. The prevalence of NAFLD in Asian cohorts is under-reported, although reaching epidemic proportions in these populations. The most well-documented NAFLD patient population is that of Caucasian ethnicity, especially from the US. The relative paucity of available literature suggests there is a vital need for more large-scale multi-ethnic clinical cohort studies to determine the incidence of NAFLD within ethnic groups. This would improve therapy and drug development, as well as help identify candidate gene mutations which may differ within the population based on ethnic background.

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          Most cited references 77

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          Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease

          Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem of unknown etiology that varies in prevalence among ethnic groups. To identify genetic variants contributing to differences in hepatic fat content, we performed a genome-wide association scan of nonsynonymous sequence variations (n=9,229) in a multiethnic population. An allele in PNPLA3 (rs738409; I148M) was strongly associated with increased hepatic fat levels (P=5.9×10−10) and with hepatic inflammation (P=3.7×10−4). The allele was most common in Hispanics, the group most susceptible to NAFLD; hepatic fat content was > 2-fold higher in PNPLA3-148M homozygotes than in noncarriers. Resequencing revealed another allele associated with lower hepatic fat content in African-Americans, the group at lowest risk of NAFLD. Thus, variation in PNPLA3 contributes to ethnic and inter-individual differences in hepatic fat content and susceptibility to NAFLD.
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            Epidemic obesity and type 2 diabetes in Asia.

            The proportions of people with type 2 diabetes and obesity have increased throughout Asia, and the rate of increase shows no sign of slowing. People in Asia tend to develop diabetes with a lesser degree of obesity at younger ages, suffer longer with complications of diabetes, and die sooner than people in other regions. Childhood obesity has increased substantially and the prevalence of type 2 diabetes has now reached epidemic levels in Asia. The health consequences of this epidemic threaten to overwhelm health-care systems in the region. Urgent action is needed, and advocacy for lifestyle changes is the first step. Countries should review and implement interventions, and take a comprehensive and integrated public-health approach. At the level of primary prevention, such programmes can be linked to other non-communicable disease prevention programmes that target lifestyle-related issues. The cost of inaction is clear and unacceptable.
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              Asians are different from Caucasians and from each other in their body mass index/body fat per cent relationship.

              The objective was to study the relationship between body mass index (BMI) and body fat per cent (BF%) in different population groups of Asians. The study design was a literature overview with special attention to recent Asian data. Specific information is provided on Indonesians (Malays and Chinese ancestry), Singaporean Chinese, Malays and Indians, and Hong Kong Chinese. The BMI was calculated from weight and height and the BF% was determined by deuterium oxide dilution, a chemical-for-compartment model, or dual-energy X-ray absorptiometry. All Asian populations studied had a higher BF% at a lower BMI compared to Caucasians. Generally, for the same BMI their BF% was 3-5% points higher compared to Caucasians. For the same BF% their BMI was 3-4 units lower compared to Caucasians. The high BF% at low BMI can be partly explained by differences in body build, i.e. differences in trunk-to-leg-length ratio and differences in slenderness. Differences in muscularity may also contribute to the different BF%/BMI relationship. Hence, the relationship between BF% and BMI is ethnic-specific. For comparisons of obesity prevalence between ethnic groups, universal BMI cut-off points are not appropriate.
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                Author and article information

                Journal
                Diabetes Metab Syndr Obes
                Diabetes Metab Syndr Obes
                Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
                Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
                Dove Medical Press
                1178-7007
                2019
                19 March 2019
                : 12
                : 357-367
                Affiliations
                [1 ]Faculty of Life Sciences and Medicine, School of Medicine, King’s College London, London, UK, krisztina.szanto@ 123456kcl.ac.uk
                [2 ]Institute for Liver and Digestive Health, University College London, London, UK, krisztina.szanto@ 123456kcl.ac.uk
                [3 ]Institute of Child Health, University College London, London, UK
                [4 ]Department of Gastroenterology and Hepatology, Guy’s and St Thomas’ Hospital, NHS Foundation Trust, London, UK
                Author notes
                Correspondence: Krisztina B Szanto, Faculty of Life Sciences and Medicine, School of Medicine, King’s College London, London, WC2R 2LS, UK, Tel +44 750 640 1933, Email krisztina.szanto@ 123456kcl.ac.uk
                Article
                dmso-12-357
                10.2147/DMSO.S182331
                6430068
                c9c57bb9-9bc0-40d4-b54d-4c361c6f8d7f
                © 2019 Szanto et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Endocrinology & Diabetes

                nafld, steatosis, obesity, ethnicity, steatohepatitis

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