Abstract | BACKGROUND: MATERIALS AND METHODS: The present case-control study recruited total of 860 subjects, including 410 GBC patients, 230 gallstone patients and 220 controls. We examined the associations of 6 selected polymorphisms in three genes: ESR1 (rs2234693, rs9340799, rs1801132), ESR2 (rs1271572, rs1256049) and PGR (rs1042838) with GBC risk. Genotyping for all the polymorphisms was done using PCR-RFLP. Multifactor dimensionality reduction and classification and regression tree approaches were combined with logistic regression to discover high-order gene-gene interactions in hormonal pathway. RESULTS: On comparing the genotype frequency distribution in gallstone and GBC patients with that of healthy subjects, the homozygous variant genotypes of ESR1-397TT (rs2234693) polymorphism showed significant risk for developing gallstone [odds ratio: OR = 2.9] and GBC [OR = 1.8] respectively. Detailed haplotypes analysis suggested that ESR1 T( rs2234693)G( rs9340799)C( rs1801132) have significant association in conferring risk for both gallstones [OR = 2.2] and GBC [OR = 3.0]. However, the variant-containing genotypes (DI+II) of PGR (rs1042838) showed low risk in both GBC [OR = 0.4] and gallstone patients [OR = 0.4].On performing the MDR analysis, ESR1 IVS1-397C>T, ESR1 IVS1-351A>G, and ESR2-789 A>C yielded the highest testing accuracy of 0.634. These results were further supported by the CART analysis which revealed that individuals with the combined genotypes of ESR1-397 CT or TT, ESR1-351 AG or GG and ESR2 -789 AA had the highest risk for GBC [OR = 3.9]. CONCLUSION: Using multi-analytical approaches, our study showed important role of ESR1 IVS1-397C>T, ESR1 IVS1-351A>G, and ESR2-789 A>C variants in GBC susceptibility and the risk appears to be mediated through gallstone dependent pathway.
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Authors | Anshika Srivastava, Kiran Lata Sharma, Neena Srivastava, Sanjeev Misra, Balraj Mittal |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 7
Pg. e40162
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22808109
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ESR1 protein, human
- Estrogen Receptor alpha
- Estrogen Receptor beta
- Receptors, Progesterone
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Topics |
- Alleles
- Base Sequence
- Case-Control Studies
- Computational Biology
- Demography
- Epistasis, Genetic
- Estrogen Receptor alpha
(genetics)
- Estrogen Receptor beta
(genetics)
- Female
- Gallbladder Neoplasms
(genetics)
- Gallstones
(genetics)
- Genes, Neoplasm
(genetics)
- Genetic Association Studies
- Genetic Predisposition to Disease
- Haplotypes
(genetics)
- Humans
- Linkage Disequilibrium
(genetics)
- Male
- Middle Aged
- Models, Genetic
- Multifactor Dimensionality Reduction
- Polymorphism, Single Nucleotide
(genetics)
- Receptors, Progesterone
(genetics)
- Risk Factors
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