- 作者：Vishnubhotla Venkata Ravikanth* ; ravikanth.aig@gmail.com" class="auth_mail" title="E-mail the corresponding author ; Guduru Venkat Rao&dagger ; ; Bale Govardhan* ; Mitnala Sasikala* ; Chivukula Subramanyam* ; H.V. Vivekananda Murthy* ; Siddapuram Siva Prasad* ; G. Deepika&dagger ; ; Rebala Pradeep&dagger ; ; Duvvuru Nageshwar Reddy&dagger ;
- 关键词：GSD ; gallstone disease ; ABCG ; 8 ATP-binding cassette ; sub-family G (WHITE) ; member 8 ; SNPs ; single nucleotide polymorphisms ; UGT1A1 ; UDP glucuronosyltransferase 1 family ; polypeptide A1 (UGT1A1) ; ABCG6 ; ATP-binding cassette protein subfamily G ; member 6 ; LDL ; low density lipoprotein ; HDL ; high density lipoprotein ; DNA ; deoxyribose nucleic acid ; PXR ; pregnane C receptor ; SD ; standard deviation ; OR ; odds ratio
- 刊名：Journal of Clinical and Experimental Hepatology
- 出版年：2016
- 出版时间：September 2016
- 年：2016
- 卷：6
- 期：3
- 页码：216-223
- 全文大小：647 K
Methods
Plasma lipid profile, bile cholesterol, acids, and phospholipid levels were estimated in patients with gall stone disease and age, sex matched controls using standard protocols. Twenty-seven SNPs related to cholesterol and bilirubin metabolism pathway genes were genotyped in the study population using the Sequenom platform. An equilibrium phase diagram involving bile salt-phospholipid-cholesterol was generated to relate phenotype with the genotype.
Results
There were no significant differences in the lipid profiles between the patients (n = 305) and controls (n = 177). Biliary cholesterol, acids, and phospholipids were significantly different between patients and controls. Single locus analysis revealed association of variants in ABCG6, ABCG8, and UGT1A1 genes with the disease; however when correction was applied as multiple testing was done, only one variant (rs6742078) in UGT1A1 gene was found to be associated with gall stone disease. Equilibrium phase diagram suggested that few samples were in the crystal formation zone. The mutant, but not wild type or heterozygous genotype of SNPs (rs6742078 and rs887829) in UGT1A1 gene, was associated with significantly higher levels of bilirubin.
Conclusions
Higher incidence of pigment stones in South Indians could be due to raised serum bilirubin levels that may be ascribed to variant in the UGT1A1 gene involved in glucuronidation of free bilirubin.