PNPLA3基因多态性与非酒精性脂肪性肝病关系的研究进展

徐静; 辛永宁; 宣世英

PNPLA3基因多态性与非酒精性脂肪性肝病关系的研究进展

1. 青岛大学医学院消化科
2. 青岛市市立医院

基金项目:

山东省自然基金资助项目(ZR2009CM015)；国家自然基金资助项目(81170337/H0304)；

详细信息

中图分类号: R575.5
计量
- 文章访问数: 3472
- HTML全文浏览量: 12
- PDF下载量: 852
- 被引次数: 0
出版历程
- 出版日期: 2012-04-20

Polymorphisms in PNPLA3 gene is associated with non-alcoholic fatty liver disease

Research funding:

摘要

摘要: 非酒精性脂肪性肝病（NAFLD）已成为西方发达国家慢性肝病的首要病因,在我国已成为仅次于慢性病毒性肝炎的第二大肝病。但是其发病机制尚不清楚,目前仍然没有有效的治疗方式,有研究指出NAFLD与遗传、环境、精神心理因素有关,而且接触相似危险因素的个体间NAFLD的发病率差异较大,疾病进程亦不尽相同,这一事实提示遗传因素及基因多态性与NAFLD发病及进程有关。全基因组关联研究发现PNPLA3（patatin-like phospholipase domain containing 3）基因多态性与NAFLD的遗传易感性及进展有着密切的联系。本综述主要从PNPLA3的结构特征、PNPLA3基因的生物学特征及PNPLA3基因多态性与NAFLD的相关性几个方面进行探讨,从而有利于NAFLD发病机制的阐明,对NAFLD的预防和治疗提供可能。
- 多态性,单核苷酸 /
- 脂肪肝,非酒精性
Abstract: Non-alcoholic fatty liver disease (NAFLD) , is the common liver disorder in the Western world and China.However, because the pathogenesis of NAFLD is undear, there is still no effeetive treatment.Provious Studies have pointed that the occurrence of NAFLD is relative with gehetic, enuiron mental and psychological factors.Some studies suggest that genetic factors and genetic polymorphism are related to pathogenesis and development of NAFLD.The genome-wide association studies shoued that the PNPLA3 (patatin like phospholipase domain containing 3) genetic polymorphism are closely linked with NAFLD.This review form several aspects to clarify the association between polymorphism in PNPLA3 gene and development of NAFLD.
- polymorphism /
- simple nucleotide

HTML全文

参考文献(31)

[1] McCullough AJ. Pathophysiology of nonalcoholic steatohepatitis [J]. J Clin Gastroenteml, 2006, 40 (Suppl 1) : S17-S 29.

[2]Jenkins CM, Mancuso DJ, Yan W, et al.Identification, clo-ning, expression, and purification of three novel human calci-um-independent phospholipase A2familymembers possess-ing triacylglycerol lipase and acylglycerol transacylase activities[J].J Biol Chem, 2004, 279 (47) :48968-48975.

[3] He S, McPhaul C, Li JZ, et al. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis [J].J Biol Chem, 2010, 285 (9) : 6706-6715.

[4]Kershaw EE, Hamm JK, Verhagen LA, et al.Adipose triglyc-eride lipase:function, regulation by insulin, and comparison with adiponutrin[J].Diabetes, 2006, 55:148-157.

[5]Villena JA, Roy S, Sarkadi-Nagy E, et al.Desnutrin, an adi-pocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids:ectopic ex-pression of desnutrin increases triglyceride hydrolysis[J].J Biol Chem, 2004, 279 (45) :47066-47075.

[6]Lake AC, Sun Y, Li JL, et al.Expression, regulation, and tri-glyceride hydrolase activity of Adiponutrin family members[J].J Lip id Res, 2005, 46 (11) :2477-2487.

[7]Romeo S, Huang-Doran I, Baroni MG, et al.Unravelling the pathogenesis of fatty liver disease:patatin-like phos-pholipase domain-containing3protein[J].Curr Opin Lipi-dol, 2010, 21 (3) :247-252.

[8] Chen W, Chang B, Li L, et al. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease[J].Hepatology, 2010 , 52 (3) : 1134-1142.

[9] Hoekstra M, Li Z, Kruijt JK, et al. The expression level of non-alcoholic fatty liver disease-related gene PNPLA3 in hepatocytes is highly influenced by hepatic lipid status[J]. J Hepatol, 2010 , 52 (2) : 244-251.

[10] Wilson PA, Gardner SD, Lambie NM, et al. Characterization of the human patatin-like phospholipase family[J]. J Lipid Res, 2006, 47 (9) : 1940-1949.

[11] Liu YM, Moldes M, Bastard JP, et al. Adiponutrin: a new gene regulated by energy balance in human adipose tissue[J]. J Clin Endocrinol Metab, 2004, 89 (6) : 2684-2689.

[12] Moldes M, Beauregard G, Faraj M, et al. Adiponutrin gene is regulated by insulin and glucose in human adipose tissue[J]. Eur J Endocrinol, 2006, 155 (3) : 461-468.

[13]Kotronen A, Johansson LE, Johansson LM, et al.A com-mon variant in PNPLA3, which encodes adiponutrin, is asso-ciated with liver fat content in humans[J].Diabetologia, 2009, 52 (6) :1056-1060.

[14]Petersen KF, Dufour S, Feng J, et al.Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asi-an–Indian men[J].Proc Natl Acad Sci U S A, 2006, 103 (48) :18273-18277.

[15] Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity[J]. Hepatology, 2004, 40 (6) : 1387-1395.

[16]Romeo S, Kozlitina J, Xing C, et al.Genetic variation in PNPLA3confers susceptibility to nonalcoholic fatty liver dis-ease[J].Nat Genet, 2008, 40 (12) , 40:1461-1465.

[17]Sookoian S, Gustavo GO, Burgue no AL, et al.A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity[J].J Lipid Res, 2009, 50 (10) :2111-2116.

[18]Kantartzis K, Peter A, Machicao F, et al.Dissociation be-tween fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase3gene[J].Diabe-tes, 2009, 58 (11) :2616-2623.

[19] Yuan X, Waterworth D, Perry JR, et al. Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes[J]. Am J Hum Genet, 2008, 83 (4) : 520-528.

[20] Speliotes EK, Butler JL, Palmer CD, et al. PNPLA3 variants specifically confer increased risk for histologic nonalcoholic fatty liver disease but not metabolic disease[J]. Hepatology, 2010, 52 (3) : 904-912.

[21]Romeo S, Sentinelli F, Dash S, et al.Morbid obesity expo-ses the association between PNPLA3I148M (rs738409) and indices of hepatic injury in individuals of European descent[J].Int J Obes (Lond) , 2010, 34 (1) :190-194.

[22]Valenti L, Al-Serri A, Daly AK, et al.Homozygosity for the PNPLA3/adiponutrin I148M polymorphism influences liver fi-brosis in patients with nonalcoholic fatty liver disease[J].Hepatology, 2010, 51 (4) :1209-1217.

[23]Krawczyk M, Grünhage F, Zimmer V, et al.Variant adiponu-trin (PNPLA3) represents a common fibrosis risk gene:non-invasive elastography-based study in chronic liver disease[J].J Hepatology, 2011, 55 (2) :299-306.

[24]Romeo S, Sentinelli F, Cambuli VM, et al.The148M allele of the PNPLA3gene is associated with indices of liver dam-age early in life[J].J Hepatol, 2010, 53 (2) :335-338.

[25]Valenti L, Alisi A, Galmozzi E, et al.I148M patatin-like phospholipase domain-containing3gene variant and severi-ty of pediatric nonalcoholic fatty liver disease[J].Hepatolo-gy, 2010, 52 (4) :1274-1280.

[26] Johansson LE, Lindblad U, Larsson CA, et al. Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity[J]. Eur J Endocrinol, 2008, 159 (5) : 577-583.

[27] Johansson LE, Johansson LM, Danielsson P, et al. Genetic variance in the adiponutrin gene family and childhood obesity[J]. PLoS One, 2009, 4 (4) : e5327.

[28]Liang H, Cai M, Bi Y, et al.A single nucleotide polymor-phism (SNP) rs2072907in the adiponutrin gene (ADPN) was not associated with obesity and type2diabetes in Chi-nese population[J].Diabetes Res Clin Pract, 2009, 85 (3) :e37-e39.

[29] Petit JM, Guiu B, Masson D, et al. Specifically PNPLA3-mediated accumulation of liver fat in obese patients with type 2 diabetes[J]. J Clin Endocrinol Metab, 2010, 95 (12) : E430- E436.

[30]Chen W, Chang B, Li L, et al.Patatin-like phospholipase domain-containing3/adiponutrin deficiency in mice is not as-sociated with fatty liver disease[J].Hepatology, 2010, 52 (3) :1134-1142.

[31]Basantani MK, Sitnick MT, Cai L, et al.Pnpla3/Adiponutrin de-ficiency in mice does not contribute to fatty liver disease or met-abolic syndrome[J].J Lipid Res, 2011, 52 (2) :318-329.

施引文献

资源附件(0)

访问统计