The Prohibitin 3′ Untranslated Region Polymorphisms Are Associated with AML Susceptibility.

Abstract 5038

The prohibitin gene, which is located on human chromosome 17q21 encodes a certain regulatory RNA molecule responsible for inhibitory effects and the respective tumor suppressor function. Common C/T and A/G polymorphisms occur at nucleotide 10701 and 10730 respectively in the 3' untranslated region (UTR) of the prohibitin gene. Recent findings indicate that presence of at least one mutant allele within the 3' UTR prohibitin gene polymorphism causes inactivation of bioactive RNA, resulting in loss of its pro-apoptotic function and subsequent risk for malignant growth. These observations led to the hypothesis that individual carrying the prohibitin T allele has increased susceptibility to acute myeloid leukemia (AML). To assess this, we carried out a case-control study of the prohibitin genotype in 381 patients with AML and 372 healthy controls. The distribution of genotypes for the prohibitin 3' UTR polymorphism in patients with AML (P=0.79) and controls (P = 0.10) were in Hardy–Weinberg equilibrium. The prohibitin 3'UTR 10701TT genotype was associated with an increased risk for AML (odds ratios (OR)=2.6; 95 percent confidence interval (CI)=1.90 to 6.19, P = 0.031). However, the prohibitin 3'UTR 10730 polymorphism was not related to AML susceptibility. Haplotype (10701T-10730A) increased risk (OR=2.11; CI=1.28-2.94) for AML. There was a significant difference in the frequency of T-allele carriers between the patients and controls (OR=1.34; CI=1.01-1.77; P=0.046). Interestingly, AML patients having 10730GG genotype had shorter overall survival rate than those with AA and AG genotypes. In conclusion, the prohibitin 3'UTR region genotyping is valuable in assessing risk of AML and estimating prognosis.