Pandey Sachchida Nand, Dixit Manjusha, Choudhuri Gourdas, Mittal Balraj
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Int J Gastrointest Cancer. 2006;37(4):124-8. doi: 10.1007/s12029-007-9002-y.
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.
低密度脂蛋白受体相关蛋白相关蛋白(LRPAP1)插入/缺失多态性影响胆固醇稳态,可能会增加患胆结石病的风险,而胆囊癌(GBC)的发病率通常与胆石症的患病率平行。
我们旨在研究LRPAP1多态性在GBC易感性中的作用。
本病例对照研究纳入了129例经证实的GBC患者、183例胆结石患者和208例健康对照。采用聚合酶链反应-限制性片段长度多态性方法进行基因分型。
与胆结石患者相比,GBC患者中LRPAP1的D等位基因显著更高(p = 0.013;OR = 1.6,95% CI = 1.1 - 2.4)。然而,与胆结石患者相比,II基因型和I等位基因与GBC风险降低相关(p = 0.002;OR = 0.1,95% CI = 0.1 - 0.6;p = 0.013;OR = 0.6,95% CI = 0.4 - 0.8)。由于D等位基因导致的风险增加仅限于女性GBC患者(p = 0.021;OR = 1.8,95% CI = 1.1 - 3.0)。然而,观察到由于II基因型和I等位基因导致的风险降低,这也仅限于女性GBC患者(p = 0.005;OR = 0.1,95% CI = 0.1 - 0.6;p = 0.021;OR = 0.5,95% CI = 0.3 - 0.8)。将患有胆结石的GBC患者与胆结石患者进行比较时,由于存在D等位基因,患有胆结石的GBC患者中观察到高风险(p = 0.032;OR = 1.7,95% CI = 1.0 - 2.8)。然而,与胆结石患者相比,患有胆结石的GBC患者中由于I等位基因观察到低风险(p = 0.032,OR = 0.6,95% CI = 0.4 - 0.9)。
似乎“D”等位基因可能调节GBC的易感性,且该风险独立于胆结石的遗传风险。