Significant Implications of Apolipoprotein A1 (APOA1) polymorphic sequence variation in bladder cancer with its relative expression predictive for differential bladder tumor grades

Background: Apolipoprotein A1 (APOA1) is a potential biomarker due its variable concentration in different types of cancers.

Objective: We for the first time evaluated the association between APOA1 -75 G/A, +83 C/T genotypes in tandem with APOA1 protein expression in urine samples to find out risk and potential relationship for differentially expressed urinary proteins and APOA1 genotypes.

Design: The study included 108 cases of bladder tumors and 150 healthy controls that were frequency matched to cases with respect to age, sex and smoking status. Genotyping was performed by PCR-RFLP and urinary expression of APOA1 protein was done by ELISA.

Results: Bladder tumor cases were significantly associated with APOA1-75 AA genotype (p<0.05) while as APOA1+83 CT heterozygotes showed association with cases (p<0.05). The overall distribution of different haplotypes showed a marked difference between cases and controls in GT when compared with wild type GC (p<0.03). Bladder tumor cases that carried variant genotype APOA1-75AA presented more (70.0%) with higher expression (≥20ng/ml) of APOA1 urinary protein and differed significantly against wild typeGG (p=0.03). Again, in low grade bladder tumors, urinary APOA1 protein significantly presented more (52.4% vs. 15.4% high grade) with higher expression (≥20ng) while high grade tumor cases (84.6% vs. 47.5% low grade) showed lower APOA1expression (<20ng/ml) (O.R= 6.08, p=0.002).

Conclusions: We found a strong association between APOA1-75G/A and risk for bladder tumor and its relation to urinary protein expression that substantiates its possible role as a marker for risk assessment of the disease and promising diagnostic marker for different grades of malignant bladder tumors

Key Words: Bladder cancer; APOA1; Genotype; Allele; Protein expression; Haplotype