Clinical Research
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 15, 2004; 10(10): 1508-1512
Published online May 15, 2004. doi: 10.3748/wjg.v10.i10.1508
Polymorphisms at cholesterol 7α-hydroxylase, apolipoproteins B and E and low density lipoprotein receptor genes in patients with gallbladder stone disease
Zhao-Yan Jiang, Tian-Quan Han, Guang-Jun Suo, Dian-Xu Feng, Sheng Chen, Xing-Xing Cai, Zhi-Hong Jiang, Jun Shang, Yi Zhang, Yu Jiang, Sheng-Dao Zhang
Zhao-Yan Jiang, Tian-Quan Han, Guang-Jun Suo, Dian-Xu Feng, Sheng Chen, Xing-Xing Cai, Zhi-Hong Jiang, Jun Shang, Yi Zhang, Yu Jiang, Sheng-Dao Zhang, Department of Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai Institute of Digestive Surgery, Shanghai 200025, China
Author contributions: All authors contributed equally to the work.
Supported by a grant from Shanghai Science and Technology Committee in China, No. 954119027
Correspondence to: Tian-Quan Han, M.D., Ph.D., Department of Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China. digsurgrj@yahoo.com.cn
Telephone: +86-21-64373909 Fax: +86-21-64373909
Received: April 8, 2003
Revised: May 12, 2003
Accepted: May 19, 2003
Published online: May 15, 2004
Abstract

AIM: To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7α-hydroxylase (CYP7A) gene promoter, apolipoprotein (APO) B gene exon 26, APOE gene exon 4 or microsatellite polymorphism of low density lipoprotein receptor (LDLR) gene exon 18.

METHODS: Genotypes of CYP7A, APOB, APOE and LDLR genes were determined in 105 patients with GSD diagnosed by B-mode ultrasonography and 274 control subjects. Serum lipids were analyzed with HITACHI 7060 automaic biochemical analyzer.

RESULTS: Body mass index (BMI) was significantly higher in patients with GSD (24.47 ± 3.09) than in controls (23.50 ± 2.16). Plasma total cholesterol was lower in patients with GSD (4.66 ± 0.92 mmol/L) than in controls (4.91 ± 0.96 mmol/L), P < 0.01 after adjusted for age, sex and BMI. The significantly higher frequency of A allele of CYP7A gene polymorphism and X+ allele of APOB gene polymorphism was seen in GSD patients. Percentages of A allele in patients and controls were 62.86% and 54.38% (P < 0.05) and those of X+ allele 8.57% and 4.01% (P < 0.01). Subjects with A allele had significantly lower plasma total cholesterol and LDL cholesterol than subjects with CC homozygote. In a multiple variable logistic regression model, the BMI (OR = 1.13, 95%CI: 1.05-1.22), A allele (OR = 1.48, 95%CI: 1.05-2.09) and X+ allele (OR = 2.28, 95%CI: 1.14-4.59) were positively associated with GSD (P < 0.05). Plasma total cholesterol (OR = 0.69, 95%CI: 0.64-0.74) was negatively related to GSD (P < 0.05).

CONCLUSION: With an association analysis, it was determined that A allele of CYP7A gene and X+ allele of APOB gene might be considered as risk genes for GSD. These alleles are related with differences of serum lipids among subjects. Multiple-variable logistic regression model analysis showed that besides BMI, GSD was affected by polygenetic factors. But the mechanism for these two alleles responsible for GSD requires further investigations.

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