Association between the rs1800591 variation of the microsomal triglyceride transfer protein gene and the risk of nonalcoholic fatty liver disease in the elderly population

Jinhan ZHAO; Jing ZHANG; Yang ZHANG; Xiaoyi XU; Yusong GOU; Hangfei XU; Yan WAN; Jian WU

doi:10.3969/j.issn.1001-5256.2023.03.011

Volume 39 Issue 3

Mar. 2023

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Association between the rs1800591 variation of the microsomal triglyceride transfer protein gene and the risk of nonalcoholic fatty liver disease in the elderly population

DOI: 10.3969/j.issn.1001-5256.2023.03.011

1.
Third Department of Liver Disease Center, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
2.
Beijing Institute of Hepatology, Beijing 100069, China
3.
Capital University of Physical Education and Sports, Beijing 100191, China

Research funding:

Beijing Hundred Thousand Talents Project (2019A15);

Beijing Municipal Institute of Public Medical Research Development and Reform Pilot Project (2021-10)

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Corresponding author: WU Jian, wujiancupes@126.com (ORCID: 0000-0001-6690-4561)
Received Date: 2022-11-18
Accepted Date: 2023-01-06
Published Date: 2023-03-20

Abstract

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 (χ²=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.
- Non-alcoholic Fatty Liver Disease,
- Genes,
- Aged

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References(42)

References

[1]	ZHOU J, ZHOU F, WANG W, et al. Epidemiological features of NAFLD From 1999 to 2018 in China[J]. Hepatology, 2020, 71(5): 1851-1864. DOI: 10.1002/hep.31150.
[2]	National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association, Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease: A 2018 update[J]. J Clin Hepatol, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007. 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会. 非酒精性脂肪性肝病防治指南(2018年更新版)[J]. 临床肝胆病杂志, 2018, 34(5): 947-957. DOI: 10.3969/j.issn.1001-5256.2018.05.007.
[3]	LI J, YAO YS, DONG Q, et al. Characterization and factors associated with sleep quality among rural elderly in China[J]. Arch Gerontol Geriatr, 2013, 56(1): 237-243. DOI: 10.1016/j.archger.2012.08.002.
[4]	ALQAHTANI SA, SCHATTENBERG JM. NAFLD in the elderly[J]. Clin Interv Aging, 2021, 16: 1633-1649. DOI: 10.2147/CIA.S295524.
[5]	LOOMBA R, SCHORK N, CHEN CH, et al. Heritability of hepatic fibrosis and steatosis based on a prospective twin study[J]. Gastroenterology, 2015, 149(7): 1784-1793. DOI: 10.1053/j.gastro.2009.03.065
[6]	PEREIRA IV, STEFANO JT, OLIVEIRA CP. Microsomal triglyceride transfer protein and nonalcoholic fatty liver disease[J]. Expert Rev Gastroenterol Hepatol, 2011, 5(2): 245-251. DOI: 10.1586/egh.11.22.
[7]	WETTERAU JR, AGGERBECK LP, BOUMA ME, et al. Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia[J]. Science, 1992, 258(5084): 999-1001. DOI: 10.1126/science.1439810.
[8]	BRADBURY P, MANN CJ, KÖCHL S, et al. A common binding site on the microsomal triglyceride transfer protein for apolipoprotein B and protein disulfide isomerase[J]. J Biol Chem, 1999, 274(5): 3159-3164. DOI: 10.1074/jbc.274.5.3159.
[9]	GOUDA W, ASHOUR E, SHAKER Y, et al. MTP genetic variants associated with non-alcoholic fatty liver in metabolic syndrome patients[J]. Genes Dis, 2017, 4(4): 222-228. DOI: 10.1016/j.gendis.2017.09.002
[10]	MUSSO G, GAMBINO R, CASSADER M. Lipoprotein metabolism mediates the association of MTP polymorphism with beta-cell dysfunction in healthy subjects and in nondiabetic normolipidemic patients with nonalcoholic steatohepatitis[J]. J Nutr Biochem, 2010, 21(9): 834-840. DOI: 10.1016/j.jnutbio.2009.06.007.
[11]	NAMIKAWA C, SHU-PING Z, VYSELAAR JR, et al. Polymorphisms of microsomal triglyceride transfer protein gene and manganese superoxide dismutase gene in non-alcoholic steatohepatitis[J]. J Hepatol, 2004, 40(5): 781-786. DOI: 10.1016/j.jhep.2004.01.028.
[12]	CARULLI L, CANEDI I, RONDINELLA S, et al. Genetic polymorphisms in non-alcoholic fatty liver disease: interleukin-6-174G/C polymorphism is associated with non-alcoholic steatohepatitis[J]. Dig Liver Dis, 2009, 41(11): 823-828. DOI: 10.1016/j.dld.2009.03.005.
[13]	OLIVEIRA CP, STEFANO JT, CAVALEIRO AM, et al. Association of polymorphisms of glutamate-cystein ligase and microsomal triglyceride transfer protein genes in non-alcoholic fatty liver disease[J]. J Gastroenterol Hepatol, 2010, 25(2): 357-361. DOI: 10.1111/j.1440-1746.2009.06001.x.
[14]	PENG XE, WU YL, LU QQ, et al. MTTP polymorphisms and susceptibility to non-alcoholic fatty liver disease in a Han Chinese population[J]. Liver Int, 2014, 34(1): 118-128. DOI: 10.1111/liv.12220.
[15]	ALQAHTANI SA, SCHATTENBERG JM. NAFLD in the Elderly[J]. Clin Interv Aging, 2021, 16: 1633-1649. DOI: 10.2147/CIA.S295524.
[16]	ANGULO P, HUI JM, MARCHESINI G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD[J]. Hepatology, 2007, 45(4): 846-854. DOI: 10.1002/hep.21496.
[17]	WILLIAMS B, MANCIA G, SPIERING W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension[J]. J Hypertens, 2018, 36(10): 1953-2041. DOI: 10.1097/HJH.0000000000001940.
[18]	Chinese Diabetes Society. Guidelines for the prevention and control of type2 diabates in China(2017 Edition)[J]. Chin J Pract Intern Med, 2018, 38(4): 292-344. DOI: 10.19538/j.nk2018040108. 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版)[J]. 中国实用内科杂志, 2018, 38(4): 292-344. DOI: 10.19538/j.nk2018040108.
[19]	WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies[J]. Lancet, 2004, 363(9403): 157-163. DOI: 10.1016/S0140-6736(03)15268-3.
[20]	CHITTURI S, FARRELL GC, HASHIMOTO E, et al. Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines[J]. J Gastroenterol Hepatol, 2007, 22(6): 778-787. DOI: 10.1111/j.1440-1746.2007.05001.x.
[21]	WANG CE, XU WT, GONG J, et al. Research progress in the treatment of nonalcoholic fatty liver disease[J]. Clin J Med Offic, 2022, 50(9): 897-899, 903. DOI: 10.16680/j.1671-3826.2022.09.06. 王彩娥, 许文涛, 宫建, 等. 非酒精性脂肪性肝病治疗研究进展[J]. 临床军医杂志, 2022, 50(9): 897-899, 903. DOI: 10.16680/j.1671-3826.2022.09.06.
[22]	BROUWERS MC, van GREEVENBROEK MM, CANTOR RM. Heritability of nonalcoholic fatty liver disease[J]. Gastroenterology, 2009, 137(4): 1536. DOI: 10.1053/j.gastro.2009.03.065.
[23]	HUSSAIN MM, SHI J, DREIZEN P. Microsomal triglyceride transfer protein and its role in apoB-lipoprotein assembly[J]. J Lipid Res, 2003, 44(1): 22-32. DOI: 10.1194/jlr.r200014-jlr200.
[24]	KIM DH, ZHANG T, LEE S, et al. FoxO6 integrates insulin signaling with MTP for regulating VLDL production in the liver[J]. Endocrinology, 2014, 155(4): 1255-1267. DOI: 10.1210/en.2013-1856.
[25]	RAABE M, VÉNIANT MM, SULLIVAN MA, et al. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice[J]. J Clin Invest, 1999, 103(9): 1287-1298. DOI: 10.1172/JCI6576.
[26]	ZHANG Y, XIN YN, CHENG YT, et al. The association between polymorphism rs1800591 in MTTP and non-alcoholic fatty liver disease[J/CD]. Chin J Liver Dis (Electronic Version), 2015, 7(3): 77-80. DOI: 10.3969/j.issn.1674-7380.2015.03.014. 张旸, 辛永宁, 程钰婷, 等. MTTP基因rs1800591位点多态性与非酒精性脂肪性肝病的相关性研究[J/CD]. 中国肝脏病杂志(电子版), 2015, 7(3): 77-80. DOI: 10.3969/j.issn.1674-7380.2015.03.014.
[27]	LI L, WANG SJ, SHI K, et al. Correlation between MTP -493G > T polymorphism and non-alcoholic fatty liver disease risk: a meta-analysis[J]. Genet Mol Res, 2014, 13(4): 10150-10161. DOI: 10.4238/2014.
[28]	TAN J, ZHANG J, ZHAO Z, et al. The association between SNPs rs1800591 and rs3816873 of the MTTP gene and nonalcoholic fatty liver disease: A meta-analysis[J]. Saudi J Gastroenterol, 2020, 26(4): 171-178. DOI: 10.4103/sjg.SJG_201_20.
[29]	BERNARD S, TOUZET S, PERSONNE I, et al. Association between microsomal triglyceride transfer protein gene polymorphism and the biological features of liver steatosis in patients with type Ⅱ diabetes[J]. Diabetologia, 2000, 43(8): 995-999. DOI: 10.1007/s001250051481.
[30]	GAMBINO R, CASSADER M, PAGANO G, et al. Polymorphism in microsomal triglyceride transfer protein: a link between liver disease and atherogenic postprandial lipid profile in NASH?[J]. Hepatology, 2007, 45(5): 1097-1107. DOI: 10.1002/hep.21631.
[31]	RAABE M, VÉNIANT MM, SULLIVAN MA, et al. Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice[J]. J Clin Invest, 1999, 103(9): 1287-1298. DOI: 10.1172/JCI6576.
[32]	TIETGE UJ, BAKILLAH A, MAUGEAIS C, et al. Hepatic overexpression of microsomal triglyceride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein B[J]. J Lipid Res, 1999, 40(11): 2134-2139.
[33]	CUCHEL M, RADER DJ. Microsomal transfer protein inhibition in humans[J]. Curr Opin Lipidol, 2013, 24(3): 246-250. DOI: 10.1097/MOL.0b013e32836139df.
[34]	GARCÍA-GARCÍA AB, GONZÁLEZ C, REAL JT, et al. Influence of microsomal triglyceride transfer protein promoter polymorphism-493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia[J]. Pharmacogenet Genomics, 2005, 15(4): 211-218. DOI: 10.1097/01213011-200504000-00004.
[35]	GOUDA W, ASHOUR E, SHAKER Y, et al. MTP genetic variants associated with non-alcoholic fatty liver in metabolic syndrome patients[J]. Genes Dis, 2017, 4(4): 222-228. DOI: 10.1016/j.gendis.2017.09.002.
[36]	ZÁK A, JÁCHYMOVÁ M, TVRZICKÁ E, et al. The influence of polymorphism of -493G/T MTP gene promoter and metabolic syndrome on lipids, fatty acids and oxidative stress[J]. J Nutr Biochem, 2008, 19(9): 634-641. DOI: 10.1016/j.jnutbio.2007.09.001.
[37]	KARPE F, LUNDAHL B, EHRENBORG E, et al. A common functional polymorphism in the promoter region of the microsomal triglyceride transfer protein gene influences plasma LDL levels[J]. Arterioscler Thromb Vasc Biol, 1998, 18(5): 756-761. DOI: 10.1161/01.atv.18.5.756.
[38]	IQBAL J, BOUTJDIR M, RUDEL LL, et al. Intestine-specific MTP and global ACAT2 deficiency lowers acute cholesterol absorption with chylomicrons and HDLs[J]. J Lipid Res, 2014, 55(11): 2261-2275. DOI: 10.1194/jlr.M047951.
[39]	YIN HJ, LI XL, XU C, et al. Clinical characteristics and influencing factors of non-alcoholic fatty liver disease in the elderly at a district in Beijing[J]. Chin J Mult Organ Dis Elderly, 2022, 21(9): 651-654. DOI: 10.11915/j.issn.1671-5403.2022.09.141. 尹慧君, 李晓利, 徐成, 等. 北京某地区老年人群非酒精性脂肪性肝病的临床特征及影响因素[J]. 中华老年多器官疾病杂志, 2022, 21(9): 651-654. DOI: 10.11915/j.issn.1671-5403.2022.09.141.
[40]	RAJAN S, HOFER P, CHRISTIANO A, et al. Microsomal triglyceride transfer protein regulates intracellular lipolysis in adipocytes independent of its lipid transfer activity[J]. Metabolism, 2022, 137: 155331. DOI: 10.1016/j.metabol.2022.155331.
[41]	GARCÍA-GARCÍA AB, GONZÁLEZ C, REAL JT, et al. Influence of microsomal triglyceride transfer protein promoter polymorphism -493 GT on fasting plasma triglyceride values and interaction with treatment response to atorvastatin in subjects with heterozygous familial hypercholesterolaemia[J]. Pharmacogenet Genomics, 2005, 15(4): 211-218. DOI: 10.1097/01213011-200504000-00004.
[42]	di FILIPPO M, MOULIN P, ROY P, et al. Homozygous MTTP and APOB mutations may lead to hepatic steatosis and fibrosis despite metabolic differences in congenital hypocholesterolemia[J]. J Hepatol, 2014, 61(4): 891-902. DOI: 10.1016/j.jhep.2014.05.023.

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Association between the rs1800591 variation of the microsomal triglyceride transfer protein gene and the risk of nonalcoholic fatty liver disease in the elderly population

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Association between the rs1800591 variation of the microsomal triglyceride transfer protein gene and the risk of nonalcoholic fatty liver disease in the elderly population

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