@article {207576, title = {Genetic Variants in nicotinamide-N-methyltransferase (NNMT) gene are related to the stage of non-alcoholic fatty liver disease diagnosed by controlled attenuation parameter (CAP)-fibroscan.}, journal = {Journal of gastrointestinal and liver diseases : JGLD}, volume = {27}, year = {2018}, pages = {265-272}, abstract = {

BACKGROUND AND AIMS: Various genetic polymorphisms play a key-role in the pathogenesis of NAFLD and progression to NASH with fibrosis to cirrhosis. We aimed to study the association between single-nucleotide polymorphisms (SNPs) in NNMT gene, namely rs694539 and the development of different stages of NAFLD diagnosed by controlled attenuation parameter (CAP) of FibroScan Echosens{\textregistered}.

METHODS: Transient elastography (FibroScan{\textregistered}) with controlled attenuation parameter (CAP) measurement was performed in 81 NAFLD patients (35 of them with liver biopsy) and 80 non-NAFLD controls. The accuracy of CAP and FibroScan for the detection and quantification of hepatic steatosis/fibrosis, respectively, was assessed based on liver biopsy aspect. Genetic variants of NNMT gene rs694539 were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

RESULTS: According to BMI (kg/m2), among the patients, 17 (21\%) were overweight, 56 (69.1\%) obese, and 8 (9.9\%) morbidly obese. CAP and FibroScan diagnosed steatosis/fibrosis correlated significantly with liver biopsy. There was a significant association between polymorphisms of rs694539-NNMT gene and NAFLD presence and stages. The mutant type (AA-genotype) was found in 33\% NAFLD patients versus 1.2\% controls (P\<0.001), whereas the wild type (GG-genotype) was present in 21\% versus 63.8\% controls (P\<0.001). Moreover, the AA-genotype significantly correlated with the steatosis degree by CAP but not the fibrosis degree by FibroScan. Multivariate regression analysis of all the independent risk factors showed non-significant correlations with the degree of steatosis on CAP. However, by using a stepwise approach, waist circumference showed significance as an independent predictor of NAFLD.

CONCLUSIONS: Polymorphisms in rs694539-NNMT gene (mutant AA-genotype) could be a genetic risk factor for developing NAFLD and NASH (indicating susceptibility for progression and complications). Individuals with wild type (GG-genotype) are at less risk of NAFLD development. CAP and FibroScan efficiently diagnosed steatosis and fibrosis.

}, author = {Hasan, Eman M and Abd Al Aziz, Rasha A and Dina Sabry and Darweesh, Samar K. and Badary, Hedy A and Elsharkawy, Aisha and Abouelkhair, Mahmood M and Ayman Yosry} }