Association between PNPLA3 and TM6SF2 gene polymorphisms and non-alcoholic fatty liver disease patients in Kazakhstan

Background: Non-alcoholic fatty liver disease (NAFLD) is a growing burden on a global scale and considered as the most common liver disease of the 21^st century, affecting both adults and children. Genome-wide association studies (GWAS) in the field of liver diseases have made a significant contribution to the understanding of genetic background for NAFLD development. Targeted genes like PNPLA3 and TM6SF2 showed some relationship with the steatosis and hepatocellular carcinoma within NAFLD patients. In this study, we tried to analyze the frequency of PNPLA3 and TM6SF2 gene polymorphisms and their relationship to changes in instrumental and laboratory markers, the composition of the gut microbiome, the development and progression of NAFLD stage in Kazakhstan.
Materials and methods: 39 individuals were involved in this study, including 18 men and 21 women: patients with a history of heavy alcohol consumption (>20 g/day) and other specific diseases such as hepatitis B and C virus infection, etc. were excluded. The diagnosis was established based on the results of clinical assessment and laboratory-instrumental results. The microbiome composition of the large intestine was studied by semiconductor sequencing of the bacterial genome using biochips. The degree of steatosis and liver fibrosis were evaluated by fibroscanning on fibroscan touch 502. Genotyping of PNPLA3 and TM6SF2 were carried out by PCR.
Results: According to PNPLA3 genotyping: 21 patients (53.85%) were C/G, 7 (17.95%) were C/C and 11 (28.20%) were G/G. Within analyzed variables, GGT showed statistically significant difference among nucleotide variability with p-value of 0.012. Other parameters within metabolic panel also showed statistically significant difference between groups, namely, total cholesterol (p=0.036) and LDL (p=0.006). Genotyping of TM6SF2 includes 24 patients (61.54%) with C/C, 15 (38.46%) with C/T and 0 with T/T. The relationship between TM6SF2 liver function test results showed no statistically significant differences between groups. All other parameters including gut microbiome analysis are not statistically significant.
Conclusions: In this study, C/G genotype possesses the highest risk and GGT along with LDL were the statistically significant parameter between them in PNPLA3 gene. TM6SF2 and gut microbiome analysis did not reveal any statistically significant differences. Additional studies with larger sample size are recommended to obtain for more detailed and sensitive results.