Genetic polymorphism of ion channel transient receptor Potential membrane melastatin and risk of benign Prostate hyperplasia among men in Kisumu County
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Date
2024-09
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Kenyatta University
Abstract
Benign prostate hyperplasia (BPH) is a condition that primarily affects middle-aged and older men, leading to lower urinary tract symptoms. The current understanding of genetic polymorphisms in transient potential membrane Melastatin channels provides compelling evidence of their potential role in the pathogenesis of BPH due to cation imbalances. This study aimed to determine the genetic polymorphism of transient receptor potential Melastatin channel genes as a risk factor for BPH among men in Kisumu County. The analytical cross-sectional study involved 194 BPH patients and 194 healthy controls aged 35 years and above from the urology clinic of Jaramogi Oginga Odinga Teaching and Referral Hospital. Six SNP variants were analyzed: TRPM2 (rs168355), TRPM6 (rs4745363), TRPM7 (rs8042919, rs2362295), and TRPM8 (rs10490018, rs1016062). DNA extraction was performed using the Qiagen® kit, and genotyping was done using the Illumina® I Scan Infinium and Multiplex human genotyping microarrays. Polymorphisms were analyzed in genome studio software modules, while haplotype distribution was determined using the DRAGEN haplotype variant. Serum concentrations of sodium, chloride, and potassium ions were measured using the ROCHE® AVL 9180, and concentrations of magnesium and bicarbonate ions were measured using the COBAS® integra 400 plus. Prostate surface antigen (PSA) was analyzed using the Cobas® e411 analyzer. Statistical significance was set at p<0.05, with 95% confidence intervals. Approval for the study was obtained from Kenyatta University's graduate school, Jaramogi Oginga Odinga Teaching and Referral Hospital's Ethics and Research Committee (IERC/JOOTRH/531/21), and NACOSTI (NACOSTI/0/22/17031). Three hundred eighty-eight adult males participated in the study: 194 BPH patients and 194 healthy individuals. The mean age for BPH patients was 65.47±12.55 years (range: 38-92 years), while the healthy control group had a mean age of 64.52±12.19 years (range:
39-91 years). Most of both groups fell within the 70-79 age range (n=53 for BPH, n=52 for controls). Statistically significant differences were found in symptom duration (p=0.001*) and severity of lower urinary tract symptoms (LUTS) (p<0.001*) between the BPH patients and controls, as well as in the association between age distribution and PSA levels (p<0.001*). Significant associations were also found between the genotypes TT/TG/GG of TRPM2 rs168355 and LUTS IPSS scores (mild, moderate, severe) (p=0.021), as well as between the genotypes CC/CT/TT of TRPM7 rs2362295 and LUTS IPSS scores (p=0.034). Additionally, significant relationships were observed between genotypes TT/TG/GG of TRPM2 rs168355 and PSA levels (p=0.034) and between CC/CT/TT of TRPM7 rs2362295 and PSA levels (p=0.041) among BPH patients. A significant correlation (p<0.05) was observed between rs168355 (TRPM2) and rs2362295 (TRPM7) polymorphisms. For rs168355, there was an increase in the TT genotype (92.7%) and T allele frequency (95.6%) in BPH patients compared to controls (TT, 61.6%; T, 74.9%; p<0.001). The GG genotype had a lower frequency among BPH patients (1.6%) compared to controls (11.9%, p<0.001). The TT/TG/GG genotypes and T/G alleles showed significant differences between patients and controls. This study's significance lies in providing critical insights into the genetic factors contributing to BPH risk, which may guide future diagnostic and therapeutic strategies aimed at improving patient outcomes
Description
A thesis submitted in fulfillment of the requirement for the degree of doctor of philosophy in medical laboratory Science (clinical chemistry) in the School of Health Sciences of Kenyatta University September 2024
Supervisors:
Dr. Nelson Menza
Dr. Rodgers Norman Demba