Abstract
BACKGROUND
Non-alcoholic fatty liver disease (NAFLD) is a leading cause of hepatic damage. NAFLD encompasses more liver conditions, from Non Alcoholic Fatty Liver (NAFL), in which there is only a deposition of fat in the liver, to the next progressive conditions like Non Alcoholic Steatohepatitis (NASH), fibrosis, cirrhosis, and in some cases HCC.
While patients with NAFLD are mostly overweight or obese, some are lean.
In recent years there is a raising interest on genetic and epigenetic modifiers of NAFLD susceptibility and progression, in particular the PNPLA3 – rs738409 polymorphism that has been identified as the major common genetic determinant of NAFLD.
Other polymorphisms such as TM6SF2 – rs58542926, MBOAT – rs641738 and GCKR rs1260346 have also been shown to play a significant role in disease development and progression.
AIM
Aim of this study was to evaluate the prevalence of the polymorphisms PNPLA3 – rs738409, TM6SF2 – rs58542926, MBOAT – rs641738 and GCKR rs1260346 in lean subjects affected by non alcoholic fatty liver disease referred by GP to our outpatient clinic and to correlate the genetic data with clinical, anthropometric and biochemical data.
METHODS
All the study subjects had anthropometric measurements including body weight, body height, waist and hip circumferences. Body mass index (BMI) was calculated as body weight (kg) divided by height (m) squared. Blood tests for liver biochemistry, glucose and lipids as well as genetic analysis were taken after at least 8 h of fasting.
They also underwent Abdomen US with FLI measurement as well as Liver stiffness measurement with FIB metavir . Also the FIB 4 and APRI score were calculated.
RESULTS
In our population the gender was equally distributed being the ratio M/F= 1,09 and mean age was 51,74 ± 13,01 years . Regarding anthropometrical data mean weight was 79,98 ± 15,04 kg, height 167,04 ± 9,19 cm with a BMI 28,60 ± 4,52 Kg/m².
- Dividing patients in two subgroups according to their BMI. We observed significant differences in the anthropometrical data as well as in the glycol-metabolic profile and in the prevalence of steatosis,in the scores FIB-4 and APRI (greater in the BMI≥25 group)
- Lean NAFLD patients were 21.1% of the total study population (n= 76 /357) with BMI: 23,87 ± 2,38 kg/m2 , Waist: 86,61 ± 11,85 cm .
-The prevalence of polymorphisms PNPLA3 – rs738409, TM6SF2 -rs58542926, MBOAT – rs641738 and GCKR rs1260346 was for :
• PNPLA3 – rs738409: G/G (39,3); C/G( 53.5); C/C(7); Allelic Frequency (AF) 66,07%;
• TM6SF2 -rs58542926: T/T(78,6): C/T (10,7); C/C (10,7);
• MBOAT – rs641738: T/T (35,7); C/T (50); C/C (14,3);
• GCKR rs1260346: T/T (14,4); C/T (3,5); C/C (82,1).
CONCLUSION
We observed a high prevalence of the studied polymorphisms in our selected population of lean NAFLD patients. Our results are in accordance con data observed in the recent literature. However these data are preliminary and need be integrated in the future. As future perspectives we think it will be valuable to increase the number of patients as well as genotype and match them also with NAFLD patients with BMI greater than 25 kg/m² and with healthy controls. We think also that it will be interesting to match lean NAFLD patients genetic data with an identical group except for BMI.
|
