Analysis of MHC microsatellites (MS) in children with acute leukemia (AL) and down syndrome (DS)

#189 ANALYSIS OF MHC MICROSATELLITES (MS) IN CHILDREN WITH ACUTE LEUKEMIA (AL) AND DOWN SYNDROME (DS) Hilario Flores,1 Carmen Alaez,1 Felicitas Manzanares,1 Araceli Rodriguez,1 Juan M. Mejia,2 Clara Gorodezky.1 1Dept. Immunogenetics, InDRE; 2IMSS, Mexico City AL may be the result of complex interactions between host genetic factors and environmental carcinogens. DS children are susceptible to the development of AL (OR!15-50). Few data exist on MHC and DS; but a high prevalence of autoimmune hypothyroidism exists in DS and children with DQA1*0301 are particularly at risk, implying an interaction between effects on ch. 21 and HLA in susceptibility (S). Analysis of MS will clarify if MHC genes facilitate the development of AL in DS, or if HLA susceptibility to AL is independent of this karyotype. We included 24 children with DS"AL; 96 with DS only; 95 with AL and 92 healthy controls; DS cases were selected from “the J.L. Down Institute”. Geneticists diagnosed the 21 trisomy. Typing of nine MS was done on DNA samples according to the 13th IHW protocols: D6S291, DQCAR, D6S273, TNFd, MIB, D6S265, D6S2222, D6S2223, D6S2239. PCR products were labeled with HEX, FAM or TET and analyzed in an ABI310 Sequencer. GeneScan software was used for interpretation. Allele frequencies were calculated. Several regions are implicated in susceptibility to AL in children: One close to HLA-DP locus (D6s291*172, pc!0.00006, OR!2.3; was significantly increased). D6s2223, (#2.5 cM telomeric to HLA-F) showed an S allele, *172, pc!6$10-12, OR! 3.8; and one linked to protection (P) to AL(*170, pc!7$10%9; OR!0.15). In children with DS"AL, the frequency of D6s291*180 was increased (pc!0.006; OR!7.5), suggesting that HLA genes are also interacting with the abnormality in ch. 21 to enhance susceptibility to AL. Genes close to D6s2223 may also be implicated: (S:*170, pc!0.03, OR!4.5); (P:*172, pc!0.0002, OR!0.27). Gene complexity is being further explored to learn more on the poligenicity of AL and its significance in DS