IMBICE   05372
INSTITUTO MULTIDISCIPLINARIO DE BIOLOGIA CELULAR
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Testing for linkage desequilibrium: NAT2 gene variants in 40 Argentine familias from 7 ECLAMC hospitals
Autor/es:
MR SANTOS, JS LÓPEZ-CAMELO, I ORIOLI, NO BIANCHI, G BAILLIET
Lugar:
Río de Janeiro, Brasil
Reunión:
Conferencia; 3th International Conference on Birth Defects and Disabilities in Developing World; 2007
Institución organizadora:
ECLAMC, RELAGH
Resumen:
Human N-acetyltransferase genes encode enzymes that metabolize hydrazines and
arylamines from the environment and diet. Functional NATs are present before birth, which
suggests that biotransformation of aromatic amines in the mother and the fetus can
contribute to the potential fetal toxicity of aromatic amines. Furthermore, acetylation of
endogenous substrates is required in order to reach normal embryonic development.
We have a special interest in NAT2 gene, since its status can be clearly assigned by
genotype and there is excellent genotype-phenotype correlation. Isolated cleft lip with or
without cleft palate (CL/P) is hereditary in a multifactorial trials; several candidate genes
have been studied in order to describe the genetic susceptibility for this malformation. Our
study evaluated linkage disequilibrium of low metabolizing genotypes by NAT2 in 40 caseparent
trios using unrelated affected cases from ECLAMC Argentina. We analyzed *4, *5,
*6 and *7 alleles for NAT2 by PCR-RFLP. We tested transmission disequilibrium using
TDT method. We found relationship between *5 low metabolizing allele and CL/P
(OR=1.7 (0.691-4.177)). Using log-linear model we measured maternal and child effects
considering only presence or absence of *5 allele in 76 complete and incomplete
triads. LEM software and EM algorithm were used to analyze missing data. OR was 2.99
(1.10- 10.39) for homozygous *5 genotype child and CL/P, with recessive transmission
and no influence of mothers genotype.
These findings prove that *5 allele is predominant but not statistically significant higher in
cases of CL/P. We expect that this comparison would turn into significant if sample size of
case-parents trios were increased.
TDT method. We found relationship between *5 low metabolizing allele and CL/P
(OR=1.7 (0.691-4.177)). Using log-linear model we measured maternal and child effects
considering only presence or absence of *5 allele in 76 complete and incomplete
triads. LEM software and EM algorithm were used to analyze missing data. OR was 2.99
(1.10- 10.39) for homozygous *5 genotype child and CL/P, with recessive transmission
and no influence of mothers genotype.
These findings prove that *5 allele is predominant but not statistically significant higher in
cases of CL/P. We expect that this comparison would turn into significant if sample size of
case-parents trios were increased.
NAT2 by PCR-RFLP. We tested transmission disequilibrium using
TDT method. We found relationship between *5 low metabolizing allele and CL/P
(OR=1.7 (0.691-4.177)). Using log-linear model we measured maternal and child effects
considering only presence or absence of *5 allele in 76 complete and incomplete
triads. LEM software and EM algorithm were used to analyze missing data. OR was 2.99
(1.10- 10.39) for homozygous *5 genotype child and CL/P, with recessive transmission
and no influence of mothers genotype.
These findings prove that *5 allele is predominant but not statistically significant higher in
cases of CL/P. We expect that this comparison would turn into significant if sample size of
case-parents trios were increased.