Nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome occurring when fat is deposited (steatosis) in the liver; but not due to excessive alcohol use, or viral (HBV and HCV) infection. It is characterized by a disease spectrum ranging from steatosis to steato-hepatitis (steatosis in addition to necro-inflammation), cirrhosis and hepatocellular carcinoma (HCC) (Wilfred de Alwis and Day 2008; Cohen et al. 2011). NAFLD prevalence is 20–30% in North America and Western countries, where it is related to modern lifestyle with additional complication due to rising incidence of type 2 diabetes mellitus (DM) and obesity (Angulo and Lindor 2002; Williams 2006; Torres and Harrison 2008). There is also substantial ethnic and temporal variability in prevalence. In Dallas Heart Study, hepatic steatosis was found in 45% of Hispanics, 33% of Caucasians and 24% of African Americans (Browning et al. 2004; Cohen et al. 2011). Epidemiological studies suggest prevalence of NAFLD to be around 17–32% in urban populations of India (table 1), with higher prevalence in those with obesity and diabetes. In rural India the prevalence is 9% (Das et al. 2010; Duseja 2010). NAFLD is a common and genetically complex disorder with an estimated heritability of 39% (Schwimmer et al. 2009). Several candidate genes studies and three genomewide association studies (GWAS) have been performed to identify the associated genes for NAFLD (Cohen et al. 2011; Hernaez 2011). There is evidence that while disease associated with single nucleotide polymorphisms (SNPs) are not significantly more differentiated between populations than random SNPs in the genome on average, risk allele frequencies do show substantial variation across human populations and may account for differences in disease prevalence between human populations (Guthery et al. 2007; Myles et al. 2008). This is even more important in the Indian context as ethnic diversity in India is immense (Indian Genome Variation Consortium 2008; Reich et al. 2009). Linguistically, Indians can be divided into Indo-European, Austro-Asiatic, Tibeto-Burman and Dravidian speakers. Historically, the Hindu caste populations are organized into four social rungs or strata, with Brahmins occupying the highest rung (upper caste) Although the ethnic groups within and across social rungs have been, by and large, genetically isolated due to centuries of endogamy, the nature and extent of admixture across social rungs have been variable (Majumder 1998; Bamshad et al. 2001; Roychoudhury et al. 2001). The 20 populations selected in this study are representative of the ethnic, linguistic and geographic diversity of India. In the present study we aimed to find out whether the Indian populations differ in risk allele frequencies (RAFs) at NAFLD-associated candidate SNPs, and also to predict the genetic risk score of NAFLD in different Indian populations, as well as to compare such risk scores with other world populations.

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