ABSTRACT
BACKGROUND: Attention Deficit and Hyperactivity Disorder (ADHD) is a common childhood neuropsychiatric condition. The disorder has a multifactorial background, with heritability estimates of around 76%, suggesting an important role of genetic factors. Candidate genes include those related to dopaminergic (e.g. DRD4, DRD5, SLC6A3 and DBH)and serotoninergic (e.g.HTR1B and SLC6A4) pathways. PURPOSE: To explore the association of common polymorphisms in six genes (DRD4, DRD5, SLC6A3, DBH, HTR1B and SLC6A4) and the susceptibility to ADHD in a Colombian sample population. METHODS: trios and 152 healthy controls were recruited. Genotyping of the six polymorphisms was performed using described PCR-based protocols. A TDT analysis was used to test if there was preferential allelic transmission for any of the six polymorphisms. Additionally, a case-control analysis was performed to test for association of the serotoninergic (HTR1B and SLC6A4) polymorphisms with ADHD. RESULTS: Through the TDT analysis there was no preferential allelic transmission for any of the studied variants. Case-control analysis did not show association. CONCLUSION: This is the first study in Latin America to describe six polymorphisms in a group of patients with ADHD. There was no evidence of association for any of the studied polymorphic variants in this Colombian ADHD sample. Further research, with larger sample sizes and study of endophenotypes, is needed in this population to confirm and extend the results.
ABSTRACT
BACKGROUND: The MTHFR rs1801131A>C and rs1801133C>T variants have been analyzed as putative genetic risk factors for oral clefts within various populations worldwide. METHODS: To test the role of these polymorphisms in nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Brazilian population, we conducted a study combining a Family-Based Association Test (transmission disequilibrium test) and a structured association analysis (case-control study) based on the individual ancestry proportions. The rs1801131 and rs1801133 were initially analyzed in 197 case-parent trios by transmission disequilibrium test, and polymorphisms showing significant association with NSCL/P were subsequently studied in independent sample composed of 318 isolated samples of NSCL/P and 598 healthy controls in a case-control approach. Genomic ancestry was characterized by a set of 40 biallelic short insertion/deletion markers. RESULTS: A strong overtransmission of the T allele of rs1801133 was observed in case-parent trios of NSCL/P (p = 0.002), but no preferential parent-of-origin transmission was detected. No association of rs1801131 polymorphism with NSCL/P was observed. The structured case-control analysis supported that the T allele was significantly more frequent in the NSCL/P group (odds ratio: 1.37; 95% CI: 1.12-1.69; p = 0.002) than in the control group. Both polymorphisms were in linkage disequilibrium (D' = 0.94 and r(2) = 0.79), and haplotype-transmission disequilibrium test for allelic combination of rs1801131 and rs1801133 showed a significant overtransmission of haplotype A-T to the affected NSCL/P offspring (p = 0.001). CONCLUSION: Our findings provide evidences for the involvement of rs1801133 in the development of NSCL/P in the Brazilian population.