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4 / 7

10/7

10/9

10/10

11/10

Total

ADHD

2 (3.7)

5 (9.3)

46 (85.2)

1 (1.9)

54 (100)

Y. WANG et al.

Table 2. Genotype frequencies for DAT1 in ADHD and control groups

Transmitted

100(92.6)

8(7.4)

108(100)

No-transmitted

94(87.0)

14(13.4)

108(100)

Total

194(89.2)

22(11.2)

216(100)

NS: no significance

Table 3. HHRR analysis of DAT1 polymorphism in nuclear families with transmitted cases

__________________________________________________________

Allele

10-Repeat

No 10-Repeat

Total

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

___________________________________________________________ χ2=1.82, df=1, p=0.177

Controls

4 (6.1)

P value

NS

66 (100)

7 (10.6)

53 (80.3)

2 (3.0)

NS

NS

NS

The VNTR variants were divided into 10-repeat allele and no 10-repeat alleles (7-, 9-, and 11-repeats) for statistical analyses, since the sample size was small and the 10-repeat allele is the most common suspected allele in some studies. We used the Haplotype-based haplotype relative risk (HHRR) design to evaluate the association between ADHD and transmission of genetic polymorphisms. This robust statistical method uses the non-transmitted parental alleles as ‘controls’ for evaluating transmission of alleles and thus prevents spurious associations due to population stratification. The HHRR analysis of DAT1 polymorphism (Table 3.) suggests that the transmission of 10-repeat allele polymorphism of the DAT1 gene is not significantly associated with ADHD in the studied cases (χ2 =1.82, df =1, p>0.05).

The transmission/disequilibrium test (TDT) is a useful method to detect linkage disequilibrium between a disease and genetic markers in nuclear families consisting of parents and one or more affected offsprings. In our study, the multiple-allele TDT test was employed for the analysis of linkage between ADHD and DAT1. All homozygotes were ignored and only information from heterozygous parents was used for calculation. Twenty parents were informative, thirteen 10-repeat (480bp) alleles were transmitted to children, and seven were not. The calculated TDT chi-square was 1.8 (df=1, p>0.05). The result did not support that ADHD was in linkage disequilibrium with any polymorphism of the DAT1 40-bp VNTR locus.

DISCUSSION

The human dopaminergic system figures prominently in the fields of neurology, psychiatry, and pharmacology.

The dopamine transporter (DAT1) gene maps to the chromosome 5 (5p15.3) and includes a variable number of tandem repeat (VNTR) polymorphisms of 40 bp in the 3’-non-coding region [25]. DAT1 plays an important role in controlling blood levels of dopamine [11,26]. It is not clear how the polymorphisms of VNTR could affect DAT1 function in the human brain. Because the VNTR locates in the 3’-non-coding region, allelic variants cannot result in

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