ABSTRACT
Objective To investigate the association between single nucleotide polymorphisms (SNP) and its haplotypes of methylenetetrahydrofolate reductase (MTHFR) gene with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastie leukemia (ALL).Methods HDMTX-treated children with ALL (1.2 to 14-years old) were selected from inpatient and followed for a retrospective study.The toxicity response of HDMTX chemotherapy was evaluated using WHO common toxicity criteria.Sixty-one patients with therapy-related toxicity and 36 patients without therapy-related toxicity were genotyped for 2 ShP (677C＞T and 1298A＞C) of the MTHFR gene by polymerase chain reaction-restriction fragment length polymorphism.Frequency of haplotypes and linkage disequilibrium of MTHFR gene were analyzed by SHEsis program.Results The distribution of MTHFR gene 677C＞T polymorphism did not appeare different between groups with or without toxicity response (x2=4.609,P=0.100),but the 1298A＞C polymorphism was significantly different (x2=10.192,P=0.006).Individuals who carried C allele (AC +CC genotype) had a decreased risk of toxicity response compared to AA genotype ( OR=0.245,95％CI:0.099-0.607,P=0.002).677C＞T and 1298A＞C polymorphisms showed strong linkage disequilibrium (D'=0.895 ).The CC haplotype was significantly associated with decreased risk of toxicity response (OR=0.338,95％CI:0.155-0.738,P=0.005),while the TA haplotype was significantly associated with the increased risk of toxicity response (OR=1.907,95％ CI:1.045-3.482,P=0.035).Conclusion MTHFR gene 1298C allele and CC haplotype might serve as protective factors while TA haplotype as a risk factor for the susceptibility to toxicity response of HDMTX chemotherapy in children with ALL.
ABSTRACT
Objective To study the epidemiological significance of community-structural difference regarding both small mammal and flea communities on Rattus ftavipectus in Dehong and Baoshan areas,Yunnan province,during 1982 to 1996.Methods Methodologies as cluster analysis,communities dominated constitution and species diversity were used for data analysis.Results 75 490 small mammals of 27 species could be divided into three types:Ⅰ.Ruili habitat-communities dominated bv R.flavipectus (54.41%)and Suncus murinus(33.37%): Ⅱ.Longchuan and Yingiiang habitat-communities dominated by R.flavipectus(62.99%),S.murinus(23.25%)and Mus musculus(10.06%);Ⅲ.Baoshan habitat-community dominated by R.flavipectus(48.07%),S.murinus(19.56%)and Crocidura attenuats(14.37%).The captured 61 122 fleas of 11 species on R.flavipectus could be divided into three types: i.Ruili habitat-communities dominated by Xenopsylla cheopis(83.51%)and Lentistivslius ferinus(13.86%);ii.Longchuan and Yingjiang habitats X.cheopis(74.42%)and L.segnis(22.94%); iii.Baoshan habitat-communities dominated by L.segnis(70.62%)and X.cheopis(22.70%).There had been 1471 strains of Y.pestis isolated from the hosts of 7 species and vectors of 5 species in Dehong areas for the ten year period.36 strains of Y.pestis were isolated from host of one species and vectors of 2 species in Baoshan area for ten years.The constitution ratio of R.flavipectus and X.cheopis was higher in Dehong area with average as 58.70%and 78.97%respectively.However.the diversities of species among host and vector communities were low,with average as 1.010 and 0.625.On the contrary,the constitution ratios of R.flavipectus and X.cheopis were lower in Baoshan area.with an average as 48.07%and 22.70%respectively but the diversities of species among host and vector community were higher with the averages as 1.471 and 0.829 respectively.The main dominative flea species from 'group ii'to 'group iii'in the flea community had changed from X.cheopis to L.segnis.Conclusion The species diversity index of host and vector community was higher in Baoshan area,while the constitution ratio of main host and vector community was lower.This findings seemed to be the important factor of the decrease of plague prevalence in Baoshan area.