Association of Genetic Polymorphisms, mRNA Expression ofp53andp21with Chronic Benzene Poisoning in a Chinese Occupational Population

Abstract

DNA damage induced by benzene reactive metabolites is thought of as an important mechanism underlying benzene hematotoxicity and genotoxicity, and genetic variation in cell-cycle control genes may contribute to susceptibility to chronic benzene poisoning (CBP). Using a case-control study that included 307 benzene-poisoned patients and 299 workers occupationally exposed to benzene in south China, we aimed to investigate the association between genetic polymorphisms of p53 and p21 and the odds of CBP. To investigate whether benzene exposure may influence mRNA expression of p53 and p21 in benzene-exposed workers, we also chose 39 CBP workers, 38 occupationally benzene-exposure workers, and 37 nonexposure workers in the same region of China. PCR-restriction fragment length polymorphism technique was applied to detect polymorphisms of p53 (rs17878362, rs1042522, and rs1625895) and p21 (rs1801270 and rs1059234), and real-time PCR was applied to detect the quantity of gene mRNA expression. We found that p21 C98A variant genotypes (CA+AA) or C70T variant genotypes (CT+TT) were associated with decreased odds of CBP [odds ratio (OR), 0.51; 95% confidence interval (95% CI), 0.32-0.83, and OR, 0.53; 95% CI, 0.29-0.95, respectively. Further analysis showed the decreased odds of CBP in the subjects with p21 CC/AT diplotype (OR, 0.51; 95% CI, 0.30-0.85). In addition, p53 mRNA expression of CBP workers or benzene-exposure workers was significantly lower than that of nonexposure workers. Although these results require confirmation and extension, our results show that polymorphisms in p21 may be protective against the risk of CBP in the Chinese occupational population. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1821-8)

P21 Gene Variation and Late-Onset Alzheimer’s Disease in the Italian Population

“…Although we could only compare the control groups, we ascertained that the allele distributions were similar to those observed by these authors. Of note is that the less frequent alleles in our sample are very rare in Europeans but are much more common in Asian populations, where they rank as the most frequent in some cases [33,34]. …”

Increased Δ133p53 mRNA in lung carcinoma corresponds with reduction of p21 expression

“…The primer sequences used were as follows: Full-length p53 , P53EX3S 5′-TCCATGGGACTGACTTTCTGC-3′ and P53EX4AS 5′-CTGGCATTCTGGGAGCTTCA-3′; Δ133p53 isoforms, P534b 5′-TAGACGCCAACTCTCTCTAG-3′ and P53RE5 5′-TTGGCAAAACATCTTGTTGAGGGC-3′; MDM-2 , MDM2S 5′-CTGAAATTTCCTTAGCTGAC-3′ and MDM2AS 5′-TTCAGGAAGCCAATTCTCAC-3′; p21 , P21S 5′-TGGACCTGTCACTGTCTTGT-3′ and P21AS 5′-TCCTGTGGGCGGATTAG-3′ and β- actin : B-ACTINS 5′-CGTCTTCCCCTCCATCGTG-3′ and B-ACTINAS 5′-CTTCTGACCCATGCCCACCA-3′. The primers were designed in our laboratory with the exception of primers P21S and P21AS, which were designed as described previously (16). All primers were synthesized by Invitrogen (Thermo Fisher Scientific, Inc.) The molecular weight of PCR products was verified by agarose gel electrophoresis.…”

Advances in Understanding Benzene Health Effects and Susceptibility

“…Thus, SNPs in genes involved in DNA repair and genomic maintenance play an important role in susceptibility to benzene-induced hematotoxicity. Other possible associations with DNA repair and genome maintenance include the recent findings that polymorphisms in the p53-dependent genes p21 and p14(ARF) may play a role in susceptibility to chronic benzene poisoning (103). …”