ABSTRACT
Objective To investigate the association between the polymorphism of the microsomal triglyceride transport protein (MTTP) gene at rs1800591 locus and the risk of nonalcoholic fatty liver disease (NAFLD) in the elderly population. Methods The clinical cohort of this study was established in Menkuang Hospital, Beijing Jingmei Group General Hospital. A total of 1098 healthy elderly volunteers were recruited for physical examination in communities in Mentougou District of Beijing, China, from January 11, 2020 to September 30, 2021, among whom there were 614 patients with NAFLD and 484 individuals without NAFLD. Gene microarray was used to determine the genotypes of MTTP rs1800591; demographic data were collected, and blood biochemical parameters were measured. The independent samples t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. The chi-square test was used to investigate whether the distribution of genotype frequency was in accordance with Hardy-Weinberg equilibrium. The unconditional logistic regression model was used to calculate odds ratio ( OR ) and its 95% confidence interval ( CI ) to investigate the association of gene polymorphism with the risk of NAFLD and other comorbidities. Results There were significant differences in sex and age between the two groups ( P < 0.05). Compared with the non-NAFLD group, the NAFLD group had significantly higher levels of body mass index (BMI), waist-hip ratio, triglyceride, alanine aminotransferase, aspartate aminotransferase, controlled attenuation parameter (CAP), and liver stiffness measurement and a significantly lower level of high-density lipoprotein (HDL) (all P < 0.05). Compared with the non-NAFLD group, the NAFLD group had a significantly higher proportion of patients with hypertension, diabetes, obesity, and metabolic syndrome (all P < 0.05). The distribution of genotype frequency at MTTP rs1800591 locus was in accordance with Hardy-Weinberg equilibrium in the control group ( χ 2 =1.097, P =0.29). There were a significant differences in the genotype and the distribution of alleles at MTTP rs1800591 locus between the patients with NAFLD and the control group (all P < 0.001). In the total population, there was a significantly lower carrying rate of T allele (GT+TT, n =351) in male individuals, and the individuals carrying T allele had significantly higher BMI and CAP than those carrying GG allele ( n =747) ( P < 0.001). Compared with the individuals who did not carry T allele, the individuals carrying T allele (GT+TT, n =232) had a significantly higher proportion of patients with obesity and a significantly lower NFS score ( P < 0.05). As for the individuals with NAFLD, the individuals carrying T allele had a significantly lower proportion of male individuals, a significantly lower waist-hip ratio, and a significantly higher level of HDL compared with those who did not carry T allele (GG, n =382), and the GT+TT group had a significantly lower NFS score than the GG group (all P < 0.05). The non-conditional logistic regression analysis showed that after adjustment for the confounding factors of sex, age, and BMI, the GT+TT genotype at MTTP rs1800591 locus significantly increased the risk of NAFLD ( OR =1.643, 95% CI : 1.226-2.203, P =0.001), and carrying T allele also increased the risk of obesity in the total population ( OR =1.371, 95% CI : 1.051-1.788, P =0.02). Conclusion MTTP rs1800591 polymorphism is associated with the development of NAFLD in the elderly population, and carrying T allele may promote hepatic steatosis and increase the risk of obesity in NAFLD, while it may inhibit the progression of liver fibrosis.
ABSTRACT
Pre-hepatic (sinusoidal) non-cirrhotic portal hypertension is a group of vascular heterogeneous diseases with portal hypertension as the prominent manifestation and has a complex etiology. Compared with the patients with cirrhotic portal hypertension, the patients with pre-hepatic (sinusoidal) non-cirrhotic portal hypertension have normal liver functions, normal or a mild increase in hepatic venous pressure gradient, and better prognosis. Pre-hepatic (sinusoidal) non-cirrhotic portal hypertension may easily be misdiagnosed as unexplained cirrhotic portal hypertension, and liver pathology is the gold standard for diagnosis. Non-selective β-receptor blockers and endoscopy are major therapies for this disease, but there is a lack of high-quality clinical evidence from large-scale prospective multicenter studies.