2013, Number 6
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Ann Hepatol 2013; 12 (6)
Genetic factors affecting susceptibility to alcoholic liver disease in an Indian population
Kumar DA
Language: English
References: 21
Page: 901-907
PDF size: 99.73 Kb.
ABSTRACT
Introduction. Indians are more likely to develop alcoholic cirrhosis compared to Caucasians, though the
cause remains obscure. North Indians tend to consume more alcohol than other parts of the country. Genetic
factors are likely to play a major role in these observations. This study investigated whether 10 different
polymorphisms were associated with alcohol dependence and/or cirrhosis in North Indians. These
were in
ADH2*2 (rs1229984),
ADH3*2 (rs698),
CYP2E1*1D, CYP2E1*5 (rs3813867 and rs2031920),
TNF-α
(rs1800629),
TNF-α (rs361525),
IL-1β (rs3087258),
CD-14 (rs2569190), IL-10 (rs1800872) and
PNPLA3 (rs738409).
Material and methods. Hundred healthy controls and 120 chronic alcoholics (60 alcoholic noncirrhotics
and 60 alcoholic cirrhotics) attending various departments of PGIMER, Chandigarh were genotyped using
PCR-RFLP methods.
Results. Alcoholic cirrhotics compared to healthy individuals demonstrated a statistically
significant increase in
PNPLA3 (10109G) allele (
p = 0.037, OR = 2.12, 95% CI 1.29-3.4). Rest of the associations
were not significant after correction for multiple testing.
Conclusion. PNPLA3 10109G predisposed North
Indian subjects to alcoholic cirrhosis.
REFERENCES
Mandayam S, Jamal MM, Morgan TR. Epidemiology of alcoholic liver disease. Semin Liver Dis 2004; 24: 217-32.
Hrubec Z, Omenn GS. Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: twin concordances for alcoholism and its biological end points by zygosity among male veterans. Alcohol Clin Exp Res 1981; 5: 207-15.
Zhu C-B, Blakely RD, Hewlett WA. The proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha activate serotonin transporters. Neuropsychopharmacol 2006; 31: 2121-31.
Douds AC, Cox MA, Iqbal TH, Cooper BT. Ethnic differences in cirrhosis of the liver in a British city: alcoholic cirrhosis in south Asian men. Alcohol Alcoholism 2003; 38: 148-50.
Khan AJ, Ruwali M, Choudhuri G, Mathur N, Husain Q, Parmar D. Polymorphism in cytochrome P450 2E1 and interaction with other genetic risk factors and susceptibility to alcoholic liver cirrhosis. Mut Res 2009; 664: 55-63.
Daly AK, Steen VM, Fairbrother KS, Idle JR. CYP2D6 multiallelism. Methods Enzymol 1996; 272: 199-210.
Das SK, Balakrishnan V, Vasudevan DM. Alcohol: its health and social impact in India. Nat Med J India 2006; 19: 94-9.
Wickramasinghe SN, Corridan B, Izaguirre J, Hasan R, Marjot DH. Ethnic differences in the biological consequences of alcohol abuse: a comparison between South Asian and European males. Alcohol Alcoholism 1995; 30: 675-80.
Sookoian S, Pirola C. Meta-analysis of the influence of I148M variant of patatin like phospholipase domain containing 3 gene (PNPLA3) on the susceptibility and histological severity of nonalcoholic fatty liver disease. Hepatology 2011; 53: 1883-94.
Tian C, Stokowski RP, Kershenobich D, Ballinger DG, Hinds DA. Variant in PNPLA3 is associated with alcoholic liver disease. Nat Genet 2010; 42: 21-3.
Stickel F, Buch S, Lau K, Zu Schwabedissen HM, Berg T, Ridinger M, Rietschel M, et al. Genetic variation in the PNPLA3 gene is associated with alcoholic liver injury in Caucasians. Hepatology 2011; 53: 86-95.
Valenti L, Rumi M, Galmozzi E, Aghemo A, Del Menico B, De Nicola S, Dongiovanni P, et al. Patatin-like phospholipase domain-containing 3 I148M polymorphism, steatosis and liver damage in chronic hepatitis C. Hepatology 2010; 53: 791-9.
Krawczyk M, Grunhage F, Zimmer V, Lamert F. Variant adiponutrin (PNPLA3) represents a common fibrosis risk gene: non-invasive elastography-based study in chronic liver disease. J Hepatol 2011; 55: 299-306.
Kato S, Shields PG, Caporaso NE, Hoover RN, Trump BF, Surgimura H, Weston A, et al. Cytochrome. P45011E1 genetic polymorphisms radical variation and lung cancer risk. Cancer Res 1992; 52: 6712-32.
Brooks PJ, Enoch M-A, Goldman D, Li T-K, Yokoyama A. The alcohol flushing response: an unrecognized risk factor for esophageal cancer from alcohol consumption. PLoS Med 2009; 6: e1000050.
Wu CF, Wu DC, Hsu HK, Kao EL, Lee JM, Lin CC, Wu MT. Relationship between genetic polymorphisms of alcohol andaldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males. World J Gastoenterol 2005; 11: 5103-8.
Grove J, Daly AK, Bassendine MF, Day CP. Association of a tumor necrosis factor promoter polymorphism with susceptibility to alcoholic steatohepatitis. Hepatol 1997; 26: 143-6.
Takamatsu M, Yamauchi M, Maezawa Y, Saito S, Maeyama S, Uchikoshi T. Genetic polymorphisms of interleukin-1beta in association with the development of alcoholic liver disease in Japanese patients. Am J Gastroenterol 2000; 95: 1305-11.
Grove J, Daly AK, Bassendine MF, Gilvarry E, Day CP. Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease. Gut 2000; 46: 540-5.
Shih H-H, Lin T-M, Chuang J-H, Eng H-L, Juo S-HH, Huang F-C, Chen CL, et al. Promoter polymorphism of the CD14 endotoxin receptor gene is associated with biliary atresia and idiopathic neonatal cholestasis. Pediatrics 2005; 116: 437-41.
Dutta AK. A New PCR-RFLP Method for Diagnosing PNPLA3 rs738409 Polymorphism . WebmedCent GENET 2011; 2: WMC002401.