title: Polymorphisms at cholesterol 7alpha-hydroxylase, apolipoproteins B and E and low density lipoprotein receptor genes in patients with gallbladder stone disease.
abstract: OBJECTIVE
  To investigate the relationship between gallbladder stone disease (GSD) and single nucleotide polymorphisms of cholesterol 7alpha-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 automatic 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
authors.forename: Zhao-Yan
authors.initials: ZY
authors.lastname: Jiang
authors.forename: Tian-Quan
authors.initials: TQ
authors.lastname: Han
authors.forename: Guang-Jun
authors.initials: GJ
authors.lastname: Suo
authors.forename: Dian-Xu
authors.initials: DX
authors.lastname: Feng
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Cai
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Jiang
authors.forename: Jun
authors.initials: J
authors.lastname: Shang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Sheng-Dao
authors.initials: SD
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001055:Apolipoproteins B / Q000235:genetics* / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D015992:Body Mass Index; D005091:Exons; D005260:Female; D042882:Gallstones / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011973:Receptors, LDL / Q000235:genetics* / Q000378:metabolism; D012044:Regression Analysis; D012189:Retrospective Studies; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism
chemical_list: D001055:Apolipoproteins B; D001057:Apolipoproteins E; D011973:Receptors, LDL; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C029009:steroid hormone 7-alpha-hydroxylase