Association of metabolic syndrome and patatin‐like phospholipase 3 – rs738409 gene variant in non‐alcoholic fatty liver disease among a Chennai‐based south Indian population

Abstract

Background Non‐alcoholic fatty liver disease (NAFLD) is commonly diagnosed in patients presenting with metabolic syndrome (MetS) and has been associated with single nucleotide polymorphisms of rs738409 in the patatin‐like phospholipase domain containing 3 (PNPLA3) gene. This association remains to be investigated in the South Indian population. We aimed to determine the association of the PNPLA3 rs738409 gene polymorphism with MetS and NAFLD among a Chennai‐based population. Methods The study comprised 105 NAFLD cases and 102 controls. All subjects were genotyped for the PNPLA3 rs738409 variant and MetS was defined according to the National Cholesterol Education Program – Adult Treatment Panel III criteria. Our case–control study showed the association of the variant with NAFLD and MetS. Results The PNPLA3 rs738409 variant was associated with NAFLD and the genotype frequencies (CC/CG/GG) were 19 (18.1%), 50 (47.6%) and 36 (34.3%) in the NAFLD group and 59 (57.8%), 29 (28.4%) and 14 (13.7%) in the control group respectively. We also confirmed the interaction between the PNPLA3 rs738409 polymorphism and MetS with respect tto elevated triglyceride levels. However, an association with elevated waist circumference, fasting glucose, blood pressure and decreased high‐density lipoprotein cholesterol was not observed in the present study. Conclusions The PNPLA3 rs738409 gene polymorphism increases the risk of NAFLD by up to four‐fold in subjects with an elevated level of triglyceride independent of other features of MetS.

Update on Non-Alcoholic Fatty Liver Disease-Associated Single Nucleotide Polymorphisms and Their Involvement in Liver Steatosis, Inflammation, and Fibrosis: A Narrative Review

“…It is unclear how the variant affects liver TG content, but it has been demonstrated that the variant is associated with the loss of TG hydrolase activities, eventually increasing intrahepatic TG accumulation [81] . Accordingly, the variant was linked to higher levels of circulating TGs, corroborating the impaired TG hydrolysis by lipoprotein lipase [21] . The hepatic fat content in individuals carrying the variant has also shown an increase in n-6 polyunsaturated fatty acids, indicating a pro-inflammatory condition that promotes de novo lipogenesis in the liver [81] .…”

“…In the end, 69 published references were selected for this study, and the summarized data are presented in Table 1. [9][10][11][12][13][14][15][16][17] Development of NAFLD [14,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] Elevated alanine aminotransferase levels [10,17,[35][36][37][38] Associated with NASH [22,[39][40][41][42][43] Associated with hepatic fat fractions [44] Associated with hepatocyte ballooning [41] Lobular and portal inflammation [41] Increased liver graft fat content [45] Elevated level of TGs [21,37] Increased liver fibrosis [13,14,…”

Association of PNPLA3 rs738409 and TM6SF2 rs58542926 Polymorphisms with Non-alcoholic Fatty Liver Disease in the Iranian Population

“…This represented two distinct groups of NAFLD for studying the genetics parameters. Globally, most studies on the associ- ation of genetic variations with NAFLD recruited their participants from clinics, indicating that the included NAFLD cases were those mostly with liver diseases rather than those with only steatosis and without inflammation or fibrosis (15,16). In studies with the recruitment of NAFLD cases with the dominance of NASH and liver fibrosis, it is obscured whether the genetic variations such as PNPLA3 rs738409 contributed to the initial development of steatosis or progression of steatohepatitis/liver fibrosis or both while studies including NAFLD cases from the general population would mostly elucidate the role of genetic markers in the initial development of steatosis, especially with subgroup analysis by steatosis and liver fibrosis degrees (17,18).…”

Patatin-like phospholipase domain-containing 3 gene (PNPLA3) polymorphic (rs738409) single nucleotide polymorphisms and susceptibility to nonalcoholic fatty liver disease: A meta-analysis of twenty studies

“…Ethnicity and country restrictions were not applied. Hotta [25] 2010 Japan N:51.7 ± 15.0 304/527 LB HB TaqMan C:47.2 ± 14.8 Wang [26] 2011 China N:48.1 ± 12.95 407/472 US HB TaqMan C:45.4 ± 15.93 Valenti [27] 2012 Italy N:49.5 ± 12 314/87 LB HB Real-time PCR C:48 ± 12 Bhatt [28] 2013 India N:38.2 ± 7.0 NA US HB Real-time PCR C:37.1 ± 6.9 Rametta [29] 2014 Italy N:49.7 ± 12.1 314/83 LB HB TaqMan C:47.7 ± 12.1 Lee [30] 2014 Korea N:44.1 ± 15.5 161/178 US HB TaqMan C:45.3 ± 10.6 Niu [31] 2014 China N:49.76 ± 16.17 373/426 US HB ABI sequencer C:47.69 ± 15.86 Shang [32] 2015 China N:11.81 ± 2.20 453/574 US PB Mass ARRAY C:11.44 ± 2.99 Vespasiani-Gentilucci [33] 2016 Italy N:51.5 ± 12.3 84/101 LB HB Sequencing C:40.1 ± 13.1 Alam [34] 2017 Bangladesh N:39.1 ± 8.6 75/99 LB HB TaqMan C:29.64 ± 7.03 Mazo [35] 2018 Brazil N:24-76 127/255 LB HB TaqMan C:19-78 Yang [36] 2018 China N:70.95 ± 4.73 158/301 US PB Real-time PCR C:72.53 ± 5.67 Costanzo [37] 2019 Italy N:11.0 ± 2.8 131/99 AMRI PB TaqMan C:9.6 ± 2.7 Hudert [38] 2019 Germany N:14.11 ± 2.15 177/93 LB PB TaqMan C:46.73 ± 16.03 Wu [39] 2020 China N:57.7 ± 8.53 NA US PB Real-time PCR C:58.90 ± 5.53 Narayanasamy [40] 2020 India N:43.15 ± 9.245 NA US PB PCR-RFLP C:41.99 ± 12.752 Lisboa [41] 2020 Brazil N:46.3 -63 77/208 LB HB Real-time PCR C:43 -61.5 Delik [42] 2020 Turkey N:46.09 ± 10 155/174 LB HB Real-time TaqMan C:44.69 ± 11.28 Akkiz [43] 2021 Turkey N:47.04 ± 12.2 NA LB HB Real-time PCR C:26.9 ± 8.6 Zhang [44] 2021 China N:38.…”