Lipoprotein Receptor Associated Protein (LRPAP1) Insertion/Deletion Polymorphism: Association with Gallbladder Cancer Susceptibility

Abstract

Low-density lipoprotein receptor-related protein associated protein (LRPAP1) insertion/deletion polymorphism influences cholesterol homeostasis and may confer risk for gallstone disease and gallbladder carcinoma (GBC) incidence usually parallels with the prevalence of cholelithiosis. We aimed to examine the role of LRPAP1 polymorphism in susceptibility to GBC. Present case control study included 129 proven GBC patients, 183 gallstone patients, and 208 healthy controls. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism method. The D allele of LRPAP1 was significantly higher in GBC patients as compared to gallstone patients (p = 0.013; OR = 1.6, 95% CI = 1.1-2.4). However, II genotype and I allele was associated with reduced risk of GBC as compared to gallstone patients (p = 0.002; OR = 0.1, 95% CI = 0.1-0.6; p = 0.013; OR = 0.6, 95% CI = 0.4-0.8) The increased risk due to D allele was limited to female GBC patients (p = 0.021; OR = 1.8, 95% CI = 1.1-3.0). However, reduced risk due to II genotype and I allele was observed which was also confined to female GBC patients (p = 0.005; OR = 0.1, 95% CI = 0.1-0.6; p = 0.021; OR = 0.5, 95% CI = 0.3-0.8). On comparing GBC patients having gallstone with gallstone patients, high risk was observed in the GBC patients having gallstone due to the presence of D allele (p = 0.032; OR = 1.7, 95% CI = 1.0-2.8). However, low risk was observed because of I allele in GBC patients with gallstone in comparison to gallstone patients (p = 0.032, OR = 0.6, 95% CI = 0.4-0.9). It appears that 'D' allele may modulate the susceptibility of GBC, and the risk is independent to genetic risk of gallstone.