title: Polymorphisms in the methylene tetrahydrofolate reductase gene and their unique combinations are associated with an increased susceptibility to the renal cancers.
abstract: OBJECTIVE
  Two single nucleotide polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene, 677C/T and 1298A/C, encode the thermolabile isoforms of the MTHFR enzyme that adversely affect the folic acid metabolic pathway. In the present study, these polymorphisms were investigated for their associations with the risk and prognosis of the renal cell carcinomas (RCCs) in Pakistani patients.
  
  
  RESULTS
  The study included 168 RCC patients and 178 controls. The polymorphisms were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method. Statistical analysis revealed that the C-allele and homozygous C genotype of the MTHFR 1298A/C polymorphism were significantly correlated with the risk of RCCs (odds ratio [OR]=1.60; 95% confidence interval [CI]=1.1-2.34 and OR=3.26; 95% CI=1.27-8.37, respectively). The combined genotype analysis showed that the 677CC+1298CC combination greatly increased the susceptibility to RCCs (OR=8.34; 95% CI=2.7-25.7). The 677CT+1298AA and 677CC+1298CA combinations were also associated with an increased risk of RCC (OR=3.21; 95% CI=1.3-7.8 and OR=2.45; 95% CI=1.3-4.6, respectively). The combined genotype effects were also evident in a semiparametric expectation-maximization-based haplotype analysis.
  
  
  CONCLUSIONS
  The results presented here indicate that the two MTHFR gene polymorphisms are significantly associated with the risk of RCCs in a cohort of Pakistani patients and may be useful as susceptibility markers in other populations of the world as well.
authors: Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation, Karachi, Pakistan.
authors: Sadia
authors: S
authors: Ajaz
authors: Shagufta
authors: S
authors: Khaliq
authors: Altaf
authors: A
authors: Hashmi
authors: Syed Ali Anwar
authors: SA
authors: Naqvi
authors: Syed Adib-ul-Hassan
authors: SA
authors: Rizvi
authors: Syed Qasim
authors: SQ
authors: Mehdi
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D010154:Pakistan; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2)