Testing for linkage desequilibrium: NAT2 gene variants in 40 Argentine familias from 7 ECLAMC hospitals

MR SANTOS, JS LÓPEZ-CAMELO, I ORIOLI, NO BIANCHI, G BAILLIET

Río de Janeiro, Brasil

Conferencia; 3th International Conference on Birth Defects and Disabilities in Developing World; 2007

ECLAMC, RELAGH

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 mother’s 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 mother’s 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 mother’s 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.