Association study between single nucleotide polymorphisms of <i>UGT</i>1<i>A</i>1 with NAFLD and serum lipids in children

ZHANG Pingping; SONG Jieyun; WANG Hui; WANG Haijun

doi:10.16835/j.cnki.1000-9817.2021.09.027

Volume 42 Issue 9

Sep. 2021

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Article Navigation > CHINESE JOURNAL OF SCHOOL HEALTH > 2021 > 42(9): 1388-1391, 1395

ZHANG Pingping, SONG Jieyun, WANG Hui, WANG Haijun. Association study between single nucleotide polymorphisms of UGT1A1 with NAFLD and serum lipids in children[J]. CHINESE JOURNAL OF SCHOOL HEALTH, 2021, 42(9): 1388-1391, 1395. doi: 10.16835/j.cnki.1000-9817.2021.09.027

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ZHANG Pingping, SONG Jieyun, WANG Hui, WANG Haijun. Association study between single nucleotide polymorphisms of UGT1A1 with NAFLD and serum lipids in children[J]. CHINESE JOURNAL OF SCHOOL HEALTH, 2021, 42(9): 1388-1391, 1395. doi: 10.16835/j.cnki.1000-9817.2021.09.027

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Association study between single nucleotide polymorphisms of UGT1A1 with NAFLD and serum lipids in children

doi: 10.16835/j.cnki.1000-9817.2021.09.027

1.
Department of Maternal and Child Health, School of Public Health, Peking University, Beijing(100191), China

Received Date: 2020-12-28
Rev Recd Date: 2021-03-08

Available Online: 2021-09-24

Publish Date: 2021-09-24

Abstract

Abstract

Objective To investigate the associations between single nucleotide polymorphisms of UDP glucuronosyltransferase Family 1 Member A1 (UGT1A1) with non-alcoholic fatty liver disease (NAFLD) and levels of serum lipids in Beijing children, and to provide scientific evidence for the study of genetic mechanism. Methods In total, 1 027 children aged 7-18 years were recruited from two primary schools and three middle schools from Haidian district of Beijing, who were randomly assigned to case group (n=162) and control group (n=865). General condition and medical history were collected by trained field health workers. Height, weight and liver ultrasound were examined. Additionally, fasting venous blood were collected to detect serum total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and alanine aminotransferase (ALT). The single nucleotide polymorphisms (SNPs) of UGT1A1 were genotyped. Binary logistic regression and multiple linear regression were applied to analyze the associations between three SNPs of UGT1A1 and NAFLD, ALT and levels of serum lipids. Results The SNP rs10929303 (C > T) of UGT1A1 was negatively associated with NAFLD(OR=0.51, 95%CI=0.32-0.83, P=0.01), while the SNP rs4148323 (G > A) was negatively associated with the serum level of TC (B=-0.10, 95%CI=-0.19--0.02, P=0.02); in addition, results were consistent regardless of whether the TC level was measured using a categorical variable or continuous variable. Conclusion The SNP rs10929303 of UGT1A1 is associated with NAFLD, and the SNP rs4148323 of UGT1A1 is associated with TC levels in Beijing children.
- Genes,
- Fatty liver,
- Dyslipidemias,
- Regression analysis,
- Child,
- Adolescent

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References(23)

References

[1]	中华医学会肝病学分会脂肪肝和酒精性肝病学组, 范建高. 非酒精性脂肪性肝病诊疗指南(2010年修订版)[J]. 中华肝脏病杂志, 2010, 18(3): 163-166. doi: 10.3760/cma.j.issn.1007-3418.2010.03.002 The Chinese National Workshop on Fatty Liver and Alcoholic Liver Disease for the Chinese Liver Disease Association of Chinese Medical Association, FAN J G. Guidelines for management of nonalcoholic fatty liver disease: an updated and revised edition[J]. Chin J Hepatol, 2010, 18(3): 163-166. doi: 10.3760/cma.j.issn.1007-3418.2010.03.002
[2]	DRAIJER L, BENNINGA M, KOOT B. Pediatric NAFLD: an overview and recent developments in diagnostics and treatment[J]. Expert Rev Gastroenterol Hepatol, 2019, 13(5): 447-461. doi: 10.1080/17474124.2019.1595589
[3]	GAGGINI M, MORELLI M, BUZZIGOLI E, et al. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease[J]. Nutrients, 2013, 5(5): 1544-1560. doi: 10.3390/nu5051544
[4]	FUJIWARA R, HAAG M, SCHAEFFELER E, et al. Systemic regulation of bilirubin homeostasis: potential benefits of hyperbilirubinemia[J]. Hepatology, 2018, 67(4): 1609-1619. doi: 10.1002/hep.29599
[5]	DELLI BOVI A P, MARCIANO F, MANDATO C, et al. Oxidative stress in non-alcoholic fatty liver disease. an updated mini review[J]. Front Med (Lausanne), 2021, 8: 595371. http://www.researchgate.net/publication/349634499_Oxidative_Stress_in_Non-alcoholic_Fatty_Liver_Disease_An_Updated_Mini_Review/download
[6]	LIN Y C, CHANG P F, HU F C, et al. Variants in the UGT1A1 gene and the risk of pediatric nonalcoholic fatty liver disease[J]. Pediatrics, 2009, 124(6): e1221-1227. doi: 10.1542/peds.2008-3087
[7]	马军, 张世伟, 邬盛鑫, 等. 不同营养状况儿童代谢综合征发生情况分析[J]. 中国学校卫生, 2008, 29(2): 103-105. doi: 10.3969/j.issn.1000-9817.2008.02.031 MA J, ZHANG S W, WU S X, et al. Prevalence of metabolic syndrome among children with different nutritional status in Beijing[J]. Chin J Sch Health, 2008, 29(2): 103-105. doi: 10.3969/j.issn.1000-9817.2008.02.031
[8]	中华人民共和国国家卫生和计划生育委员会. 学龄儿童青少年超重与肥胖筛查WS/T 586—2018[S]. 北京, 2018. National Health and Family Planning Commission of People's Republic of China. Screening for overweight and obesity among school-age children and adolescents WS/T 586-2018[S]. Beijing, 2018.
[9]	GRAIF M, YANUKA M, BARAZ M, et al. Quantitative estimation of attenuation in ultrasound video images: correlation with histology in diffuse liver disease[J]. Invest Radiol, 2000, 35(5): 319-324. doi: 10.1097/00004424-200005000-00006
[10]	EGUCHI Y, HYOGO H, ONO M, et al. Prevalence and associated metabolic factors of nonalcoholic fatty liver disease in the general population from 2009 to 2010 in Japan: a multicenter large retrospective study[J]. J Gastroenterol, 2012, 47(5): 586-595. doi: 10.1007/s00535-012-0533-z
[11]	POLYZOS S A, KOUNTOURAS J, MANTZOROS C S. Obesity and nonalcoholic fatty liver disease: from pathophysiology to therapeutics[J]. Metabolism, 2019, 92: 82-97. doi: 10.1016/j.metabol.2018.11.014
[12]	LIU D, YU Q, LI Z, et al. UGT1A1 dysfunction increases liver burden and aggravates hepatocyte damage caused by long-term bilirubin metabolism disorder[J]. Biochem Pharmacol, 2021, 190: 114592. doi: 10.1016/j.bcp.2021.114592
[13]	WANG J, YIN J, XUE M, et al. Roles of UGT1A1 Gly71Arg and TATA promoter polymorphisms in neonatal hyperbilirubinemia: a meta-analysis[J]. Gene, 2020, 736: 144409. doi: 10.1016/j.gene.2020.144409
[14]	LÉVESQUE E, GIRARD H FAU-JOURNAULT K, JOURNAULT K FAU-LÉPINE J, et al. Regulation of the UGT1A1 bilirubin-conjugating pathway: role of a new splicing event at the UGT1A locus[J]. Hepatology, 2007, 45(1): 128-138. doi: 10.1002/hep.21464
[15]	DAY C, JAMES O. Steatohepatitis: a tale of "hits"?[J]. Gastroenterology, 1998, 114(4): 842-845. doi: 10.1016/S0016-5085(98)70599-2
[16]	FANG Y L, CHEN H, WANG C L, et al. Pathogenesis of non-alcoholic fatty liver disease in children and adolescence: From "two hit theory" to "multiple hit model"[J]. World J Gastroenterol, 2018, 24(27): 2974-2983. doi: 10.3748/wjg.v24.i27.2974
[17]	MARUHASHI T, KIHARA Y, HIGASHI Y. Bilirubin and endothelial function[J]. J Atheroscler Thromb, 2019, 26(8): 688-696. doi: 10.5551/jat.RV17035
[18]	PURI K, NOBILI V, MELVILLE K, et al. Serum bilirubin level is inversely associated with nonalcoholic steatohepatitis in children[J]. J Pediatr Gastroenterol Nutr, 2013, 57(1): 114-118. doi: 10.1097/MPG.0b013e318291fefe
[19]	KUNUTSOR S K, FRYSZ M, VERWEIJ N, et al. Circulating total bilirubin and risk of non-alcoholic fatty liver disease in the PREVEND study: observational findings and a Mendelian randomization study[J]. Eur J Epidemiol, 2020, 35(2): 123-137. doi: 10.1007/s10654-019-00589-0
[20]	LUO L, AN P, JIA X, et al. Genetically regulated bilirubin and risk of non-alcoholic fatty liver disease: a mendelian randomization study[J]. Front Genet, 2018, 9: 662. doi: 10.3389/fgene.2018.00662
[21]	郭奕瑞, 张莉. 血脂异常与非酒精性脂肪肝发病关系前瞻性队列研究[J]. 中国公共卫生, 2021, 37(1): 141-144. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGGW202101036.htm GUO Y R, ZHANG L. Association between dyslipidemia and nonalcoholic fatty liver disease incidence: a prospective cohort study[J]. Chin J Public Health, 2021, 37(1): 141-144. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGGW202101036.htm
[22]	SMIDERLE L, GALVÃO A C, FONTANA C, et al. Evaluation of UGT1A1 and SULT1A1 polymorphisms with lipid levels in women with different hormonal status[J]. Gynecol Endocrinol, 2011, 27(1): 20-26. doi: 10.3109/09513590.2010.493248
[23]	CHALASANI N, YOUNOSSI Z, LAVINE J E, et al. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases[J]. Hepatology, 2018, 67(1): 328-357. doi: 10.1002/hep.29367