کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2806629 | 1157128 | 2010 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
CYP7A1 (â204 A>C; rs3808607 and â469 T>C; rs3824260) promoter polymorphisms and risk of gallbladder cancer in North Indian population
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
علوم غدد
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Cholesterol 7-α hydroxylase (CYP7A1), which is a rate-limiting enzyme for cholesterol catabolism and bile acid synthesis, may affect cholesterol homeostasis and result in gallstone formation that is a major risk factor for gallbladder cancer (GBC) pathogenesis. Genetic variations in CYP7A1 may influence its expression and thus may affect the risk of gallstone disease and GBC. We aimed to study the association of 2 promoter polymorphisms of CYP7A1 (â204 A>C [rs3808607] and â469 T>C [rs3824260]) in gallstone and GBC susceptibility in North Indian population. The study included 185 GBC patients, 195 symptomatic gallstone patients, and 200 healthy controls. Genotyping for both polymorphisms was done by polymerase chain reaction-restriction fragment length polymorphism method. Although the CC genotype of CYP7A1 â204 A>C was not significantly associated with gallstone disease (P = .083, odds ratio [OR] = 1.69, 95% confidence interval [CI] = 0.9-3.0), it was conferring higher risk for GBC (P = .018, OR = 2.05, 95% CI = 1.1-3.7). However, CYP7A1 â469 T>C was not associated with gallstone disease and GBC risk in our population. After subgroup stratifications on the basis of sex and gallstone status, CC genotype and variant allele of CYP7A1 â204 A>C imparted higher risk for GBC in women (P = .003, OR = 3.30, 95% CI = 1.5-7.2) and patients without gallstones (P = .045, OR = 1.91, 95% CI = 1.2-3.6). Haplotype analysis of the 2 polymorphisms showed that C,T (P = .045, OR = 1.84, 95% CI = 1.0-3.3) and C,C (P = .0001, OR = 3.10, 95% CI = 1.6-6.0) haplotypes had elevated risk of GBC predisposition. CYP7A1 â469 T>C is not associated with gallstone disease or GBC risk. Although CYP7A1 â204 A>C might play a modest role in gallstone susceptibility, it is an independent risk factor for GBC in North Indian population. Underlying mechanism for GBC susceptibility by CYP7A1 (â204 A>C and â469 T>C) haplotype appears to be independent of gallstone pathway and is believed to involve genotoxicity resulting from subnormal bile acid production.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Metabolism - Volume 59, Issue 6, June 2010, Pages 767-773
Journal: Metabolism - Volume 59, Issue 6, June 2010, Pages 767-773
نویسندگان
Anvesha Srivastava, Gourdas Choudhuri, Balraj Mittal,