Study Report
Basic Info
Reference |
Li J, 2006(c)16389593
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Citation |
Li J., Wang Y., Zhou R., Zhang H., Yang L., Wang B. and Faraone S. V. (2006) "Association between tryptophan hydroxylase gene polymorphisms and attention deficit hyperactivity disorder in Chinese Han population." Am J Med Genet B Neuropsychiatr Genet, 141B(2): 126-9.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
362 unrelated complete trios |
Predominant Ethnicity |
Mongoloid |
Population |
China |
Gender |
303 (83.7%) male probands and 59 (16.3%) female probands |
Age Group |
Children/Adolescents
:
6-17 years, mean age 10.3, SD=2.6 years
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Detail Info
Summary |
The current study examined the relationship between the A218C and A-6526G polymorphisms of the TPH gene and ADHD. Three hundred sixty-two unrelated ADHD probands and their biological parents were recruited to participate in this study. No biased transmission of any allele of the two polymorphisms was observed using TDT analysis. However, haplotype analyses found that the rare 218A/-6526G haplotype was significantly not transmitted to probands with ADHD, regardless of subtype. Although this finding for ADHD in the Chinese Han population. |
Total Sample |
Three hundred and sixty-two unrelated complete trios of ADHD probands and both parents were recruited from the child psychiatric clinics at Peking University Institute of Mental Health from September 1999 to April 2003. |
Sample Collection |
Han Chinese |
Diagnosis Description |
Diagnoses of ADHD and subtypes of ADHD were based on the USAn Clinical Diagnostic Interview Scales (CDIS) [Barkley, 1998], a structured interview derived from the DSMIV. Additionally, teachers completed the Rutter Scale to evaluate the children's behaviors in the school environment. Based upon data collected from the CDIS, parent interviews and teacher reports, consensus diagnoses were assigned to all probands. Of the 362 ADHD trios, 150 (41.4%) children met criteria for ADHD-C, 23 (6.4%) met criteria for ADHD-HI, and 189 (52.2%) children met criteria for ADHD-I. |
Technique |
The peripheral venous blood samples were refrigerated at 4oC in EDTA-containing test tubes. Genomic DNA was extracted using standard method within 2 weeks. A218C Polymorphism Typing: Forward primer 5'-TTCAGA TCC CTT CTA TAC CCC AGA- 3' and reverse primer 5'-GGA CAT GAC CTA AGA GTT CAT GGC A-3' were used to generate 918 bp fragments of A218C polymorphism. A 25-ul reaction was performed according to the protocol previously described [Nielsen et al., 1997] on a PE- 9700 or a PE-2400 thermal cycler (Perkin Elmer Company, Branchburg, New Jersey). After digestion, the A-variant was cut into two fragments of 860 bp and 58 bp, while the C-variant was cut into three fragments of 615 bp, 245 bp, and 58 bp. A-6526G Polymorphism Typing: Forward primer 5'-TGGCAT TGAAGTAAGAGCAC-3' and reverse primer 5'-GTT TCA TGC AGG TAT TAG TG-3' were used to generate 280 bp fragments of A-6526G polymorphism. A 25-ul reaction was performed according to the protocol previously described [Rotondo et al., 1999]. After digestion, the G-variant was un-cut, while the A-variant was cut into two fragments of 194 bp and 86 bp. |
Analysis Method |
They used the transmission disequilibrium test (TDT) to assess linkage and association of the two TPH polymorphisms with ADHD. The TDT uses the McNemar X2 test to compare the probability of transmission of parental alleles to affected offspring. The McNemar X2 test was done using SPSS (release 11.0, SPSS, Inc., Chicago, IL). They also analyzed haplotypes using the TRANSMIT program [version 2.5; Clayton, 1999]. |
Result Description |
No biased transmission of any allele of the two polymorphisms was observed using TDT analysis. However, haplotype analyses found that the rare 218A/-6526G haplotype was significantly not transmitted to probands with ADHD (X2=4.4995, P-value=0.034), regardless of subtype. Although this finding for ADHD in the Chinese Han population. |
Other variant reported by this study (count: 2)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
TPH1 promoter A-6526G |
A/G |
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TDT P-value=0.297, McNemar X2=1.086 for ADHD phen......
TDT P-value=0.297, McNemar X2=1.086 for ADHD phenotype; TDT P-value=0.263, McNemar X2=1.252 for ADHD-C phenotype; TDT P-value=0.424 for ADHD-HI phenotype; TDT P-value=0.932, McNemar X2=0.007 for ADHD-I phenotype
More...
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no biased transmission of any allele was observed |
Non-significant
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TPH1 intron7 A218C |
C/A |
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TDT P-value=0.882, McNemar X2=0.022 for ADHD phen......
TDT P-value=0.882, McNemar X2=0.022 for ADHD phenotype; TDT P-value=0.811, McNemar X2=0.057 for ADHD-C phenotype; TDT P-value=0.572, McNemar X2=0.321 for ADHD-HI phenotype; TDT P-value=0.84, McNemar X2=0.041 for ADHD-I phenotype
More...
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no biased transmission of any allele was observed |
Non-significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
TPH1 |
haplotype 218A/-6526G to the ADHD probands was significantly......
haplotype 218A/-6526G to the ADHD probands was significantly decreased, P-value=0.034, X2 =4.4995; decreased transmission of haplotype 218A/-6526G emerged in families of probands with ADHD-C, P-value=0.022, X2 =5.253
More...
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Significant
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