Significant Implications of APOA1 Gene Sequence Variations and Its Protein Expression in Bladder Cancer

Biomedicines

Arshad A. Pandith¹  Sheikh Mansoor¹  Aabid Koul¹  Iqbal Qasim¹  Shahid M. Baba¹  Wafa Charifi²  Ajaz Ahmad³  Javid A. Magray⁴  Arif Hamid⁴  Muzzain Khateeb⁴  Mohammad S. Wani⁴  Zafar A. Shah⁵ 

[1] Advanced Center for Human Genetics, SK Institute of Medical Sciences (SKIMS), Srinagar 190011, India;Cochin Institute, University of Paris, INSERM, U1016 Paris, France;Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;Department of Urology, SK Institute of Medical Sciences (SKIMS), Srinagar 190011, India;Immunology and Molecular Medicine, SK Institute of Medical Sciences (SKIMS), Srinagar 190011, India;

关键词: bladder cancer;    APOA1;    genotype;    allele;    protein expression;    haplotype;   

DOI  :  10.3390/biomedicines9080938

来源: DOAJ

【 摘 要 】

Apolipoprotein A1 (APOA1) is a potential biomarker because of its variable concentration in different types of cancers. The current study is the first of its kind to evaluate the association between the APOA1 genotypes of −75 G/A and +83 C/T in tandem with the APOA1 protein expression in urine samples to find out the risk and potential relationship for differentially expressed urinary proteins and APOA1 genotypes. 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 using PCR-RFLP and the urinary expression of the APOA1 protein was done using ELISA. Bladder tumor cases were significantly associated with the APOA1 −75 AA genotype (p < 0.05), while the APOA1 +83 C/T heterozygotes showed an association with cases (p < 0.05). The overall distribution of the different haplotypes showed a marked difference between the cases and controls in GT when compared with the wild type GC (p < 0.03). Bladder tumor cases that carried the variant genotype APOA1 −75AA were found more (70.0%) with a higher expression (≥20 ng/mL)of the APOA1 urinary protein and differed significantly against wild type GG (p = 0.03). Again, in low grade bladder tumors, urinary APOA1 protein was exhibited significantly more (52.4% vs. 15.4% high grade) with a higher expression (≥20 ng), while high grade tumor cases (84.6% vs. 47.5% low grade) showed a lower APOA1 expression (<20 ng/mL) (O.R = 6.08, p = 0.002). A strong association was observed between APOA1 −75G/A and risk for bladder tumor and its relation to urinary protein expression, which substantiates its possible role as a marker for the risk assessment of the disease and as a promising diagnostic marker for different grades of malignant bladder tumors.

【 授权许可】

Unknown