Polymorphisms at cholesterol 7α-hydroxylase, apolipoproteins B and E and low density lipoprotein receptor genes in patients with gallbladder stone disease

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.

CYP7A1 genotypes and haplotypes associated with hypertension in an obese Han Chinese population

“…Most studies concerning genetic variations in the CYP7A1 gene have focused on an A-C SNP in the promoter region, which is at position À278 from the translation initiation codon or position À204 from the transcriptional start site. The results appear to be conflicting as to whether this polymorphism is significantly associated with, for example, plasma lipid levels, 7-9 risk of arteriosclerosis 10 and gallstone disease [11][12][13] in adults and children from Caucasian and Asian populations. Some intervention trials have suggested that the polymorphism has an important role in the metabolism of lipids.…”

Fibroblast growth factor receptor 4 Gly388Arg polymorphism associated with severity of gallstone disease in a Chinese population

“…Recent human genetic studies have indicated that genes involved in bile salt balance, including cholecystokinin A receptor and CYP7A1, are susceptibility genes for gallstone disease (Miyasaka et al, 2002;Jiang et al, 2004). Compared to the Gly388 variant, the Gly388Arg (G-388R) variation in the transmembrane domain (exon 9) of the FGFR4 protein results in FGFR4 stabilization and increasing phosphorylation after ligand binding (Wang et al, 2008).…”

Associations between Lifestyle-Related Diseases and Transporters Involved in Intestinal Absorption and Biliary Excretion of Cholesterol

“…For instance, hereditary contribution of cholesterol 7α-hydroxylase and apolipoprotein E and B genes to gallstone formation were reported. 84,85) In addition, as described above, based on the fact that hypersecretion of cholesterol into bile has been identified as the primary pathogenic event in gallstone formation, 86) gene mutations and single nucleotide polymorphisms (SNPs) of ABCG5 and ABCG8 have attracted considerable attention. To date, several SNPs of ABCG5 and ABCG8 were reported to be associated with cholesterol gallstone disease.…”