Reply to Ostrovosky et al.

Reply to Winter et al.

“…Their initial study, 3 included healthy individuals from four Israeli Jewish populations (Ashkenazi, North African, Mediterranean and Near Eastern). The allele frequencies for the Arg307Lys SNP were similar in each of these populations and comparable to our data for healthy individuals in the Northern Ireland population (Arg/ Lys; 74.44/25.56%) 2 and to allele frequencies for European populations listed on the NCBI SNP database. 5 In their subsequent study, 4 Ostrovsky et al 1 point out that the healthy control group included the four Israeli Jewish populations mentioned above plus individuals from other Jewish and non-Jewish populations.…”

“…As stated by Ostrovsky et al, 1 their patient and control populations were heterogeneous, including individuals from several Jewish and non-Jewish ethnic groups. In contrast, all of the patient and control individuals included in our study 2 were of Northern Irish origin. Due to its geographical isolation and historically low levels of inward migration, the population of Northern Ireland may be considered to be genetically more homogeneous relative to other populations, such as the Israeli population, studied by Ostrovosky et al As such, we suggest that the influence of genetic factors predisposing to complex conditions, such as ALL, may be more apparent in our population.…”

“…In conclusion, we consider that a degree of uncertainty remains concerning the frequency of the Arg307Lys SNP in the population studied by Ostrovosky et al 4 Furthermore, we suggest that the relative genetic homogeneity of the Northern Ireland population included in our study lends weight to our findings. The lack of the results of replication 1,2 in different studies is a very complicated problem. Recently, this question regarding gene-disease association studies was analyzed by Moonesinghe et al 3 Nonreplication may be the result of population stratification, phenotype misclassification, genotyping error, selection biases and differences in genetic effects that include differential linkage disequilibrium of the identified genetic markers with culprit gene variant, population-specific genegene or gene-environment interactions.…”

“…We appreciated Dr Bergsagel's thoughtful editorial 1 accompanying our paper on the long-term survival of patients in whom metaphase cytogenetic abnormalities were effectively suppressed. 2 We wish to put that work in the context of almost 20 years of clinical trial and translational research in multiple myeloma at the University of Arkansas for Medical Sciences.…”