Hubungan Antara Polimorfisme Gen Dopamine Receptor D4 (DRD4) Dan Gen Dopamine Transporter 1 (DAT1) Dengan Gambaran Neurologis Dan Neuropsikologi Pada Anak Dengan Attention Deficit/Hyperactivity Disorder (ADHD

Cempaka Thursina Srie Setyaningrum, rof. Dr. dr. Sri Sutarni, SpS(K); Prof. Dr. dr. Samekto Wibowo, SpS(K), SpFK

2015 | Disertasi | S3 Kedokteran Umum

Background. Attention Deficit/Hyperactivity Disorder (ADHD) is a pediatric neurobehaviour disorder caused by various factors, among them are genetic factors. Among these genetic factors, the most frequently associated genes were dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) genes. The effects of particular genetic patterns on the clinical and neuropsychological features are still largely unknown. The objective of this study is to find the association between polymorphism gen DRD4 and DAT1 with ADHD, and their influences on the clinical and neuropsychological features in children with ADHD in Yogyakarta area. Methods. Sixty-five ADHD children and 70 controls went through genetic, clinical, neurological and neuropsychological studies by using these questionnaires, SPPAHI, ACTRS, ACPRS, DSM IV, WISC II, MMMSEC, Stroop Test, preceded by a reliability test. These results were scored quantitatively. DAT1 and DRD4 genetic profiles were analyzed by PCR. Results were significant if p<0.05 Results. DRD4 VNTR 7 Repeat allelic pattern was not found in the current study, while 2R allelle (ADHD group 66.2%; control group 63.4%) and DAT1 VNTR 10Repeat allele (ADHD 90.3%; controls 85.2%)were the most common patterns, these genes were not associated with ADHD (DRD4 gene p = 0.926; DAT1 gene p = 0.830), nor its subtypes (DRD4 gene p = 0.102; DAT1 gene p = 0.916), DAT1 9/10R allele were significantly associated with VIQ scores while DRD4 2R did not affect the clinical and neuropsychological profiles. Bivariate analyses suggested parenting style p<0.001, family income p<0.001 (2.013 -79.739), a history of LBW p < 0.001 (3.075-24.426), nutritional history of BGM p = 0.004 (1.548-15.830), a history of hyperactivity p=0.011 (1,176-7.572) and a history of antisocial p=0.003 (1.484-7.572), were significant risk factors for ADHD. There were clinical and neuropsychological profile differences between ADHD and controls groups, MMMSEC orientation sub-score p<0.001 (9.98 +-1.192: 11.10 +-1.079), registration sub-score p = 0.004 (2.69 +-0.498: 2.90 +-0.302) , recall / memory p = 0.002 (2.63 +-0.651: 2.91 +-0.371), language sub-score p<0.001 (+-1.389 10.91: 11.69 +-0.713), total MMMSEC score p<0.001 (32.98 +-2.414: 35.39 +-1.875), VIQ p<0.001 (103.18 +-15.155: 114.27 +- 12.748), FIQ p<0.001 (101.06 +-13.087: 108.63 +-10.685), SPPAHI p<0.001 (97, 91 +- 11,468: 39.23 +-20.3314), ACPRS p<0.001 (14.98 +-3.435: 6.14 +-2.994), ACTRS p<0.001 (15.5 +-3.749: 5.39 +-3.719), NST p< 0001 (25.28 +-3.79: 18.41 +-3.25), IST p = 0.02 (34.90 +-8.13: 28.87 +-4.17), NST error p<0.001 (1.79 +-1.23: 1.23 +-0.42), IST error p = 0.02 (2.3 +- 1.86: 1.86 +-0.75), percentage NST error p = 0.05 (60.42%: 42.94%), percentage IST error p = 0.05 (68.53%: 50.71%), NST correct p = 0.02 (22.54 +-1.68: 16.27 +-1.772), IST correct p<0.001 (27.18 +-2.44: 24.47 +-2.76), and restless leg syndrome p = 0006. Results of analysis in ADHD subtypes on the clinical and neuropsychological found significant differences in MMMSEC orientation sub-score p=0.016; language sub-score p = 0.029; and total score p = 0.027, FIQ p<0.001, SPPAHI score p=0048. Multivariate analysis found that parenting style p<0.001 (7.574 - 428.293), family income p<0.001 (10.359 -390.772), and nutritional history of BGM p = 0.029 (1.325 - 203.234), were independent risk factors for ADHD. Conclusions. 10R DAT1 polymorphism frequency were higher in Yogyakarta area than other countries, 7R DRD4 alleleic pattern was not found while the most common were 2R DRD4, 9/10R DAT1 polymorphism were significantly associated with VIQ score, whereas polymorphism gen DRD4 2R and DAT1 10R were not associated with AHD and also with the particular clinical and neuropsychological features, there were no differences in the proportion of 10R DAT1 allele and 2R DRD4 allele between ADHD subtypes and there were

Background. Attention Deficit/Hyperactivity Disorder (ADHD) is a pediatric neurobehaviour disorder caused by various factors, among them are genetic factors. Among these genetic factors, the most frequently associated genes were dopamine receptor D4 (DRD4) and dopamine transporter 1 (DAT1) genes. The effects of particular genetic patterns on the clinical and neuropsychological features are still largely unknown. The objective of this study is to find the association between polymorphism gen DRD4 and DAT1 with ADHD, and their influences on the clinical and neuropsychological features in children with ADHD in Yogyakarta area. Methods. Sixty-five ADHD children and 70 controls went through genetic, clinical, neurological and neuropsychological studies by using these questionnaires, SPPAHI, ACTRS, ACPRS, DSM IV, WISC II, MMMSEC, Stroop Test, preceded by a reliability test. These results were scored quantitatively. DAT1 and DRD4 genetic profiles were analyzed by PCR. Results were significant if p<0.05 Results. DRD4 VNTR 7 Repeat allelic pattern was not found in the current study, while 2R allelle (ADHD group 66.2%; control group 63.4%) and DAT1 VNTR 10Repeat allele (ADHD 90.3%; controls 85.2%)were the most common patterns, these genes were not associated with ADHD (DRD4 gene p = 0.926; DAT1 gene p = 0.830), nor its subtypes (DRD4 gene p = 0.102; DAT1 gene p = 0.916), DAT1 9/10R allele were significantly associated with VIQ scores while DRD4 2R did not affect the clinical and neuropsychological profiles. Bivariate analyses suggested parenting style p<0.001, family income p<0.001 (2.013 -79.739), a history of LBW p < 0.001 (3.075-24.426), nutritional history of BGM p = 0.004 (1.548-15.830), a history of hyperactivity p=0.011 (1,176-7.572) and a history of antisocial p=0.003 (1.484-7.572), were significant risk factors for ADHD. There were clinical and neuropsychological profile differences between ADHD and controls groups, MMMSEC orientation sub-score p<0.001 (9.98 +- 1.192: 11.10 +- 1.079), registration sub-score p = 0.004 (2.69 +- 0.498: 2.90 +- 0.302) , recall / memory p = 0.002 (2.63 +- 0.651: 2.91 +- 0.371), language sub-score p<0.001 (+- 1.389 10.91: 11.69 +- 0.713), total MMMSEC score p<0.001 (32.98 +- 2.414: 35.39 +- 1.875), VIQ p<0.001 (103.18 +- 15.155: 114.27 +- 12.748), FIQ p<0.001 (101.06 +- 13.087: 108.63 +- 10.685), SPPAHI p<0.001 (97, 91 +- 11,468: 39.23 +- 20.3314), ACPRS p<0.001 (14.98 +- 3.435: 6.14 +- 2.994), ACTRS p<0.001 (15.5 +- 3.749: 5.39 +- 3.719), NST p< 0001 (25.28 +- 3.79: 18.41 +- 3.25), IST p = 0.02 (34.90 +- 8.13: 28.87 +- 4.17), NST error p<0.001 (1.79 +- 1.23: 1.23 +- 0.42), IST error p = 0.02 (2.3 +-1.86: 1.86 +- 0.75), percentage NST error p = 0.05 (60.42%: 42.94%), percentage IST error p = 0.05 (68.53%: 50.71%), NST correct p = 0.02 (22.54 +- 1.68: 16.27 +- 1.772), IST correct p<0.001 (27.18 +- 2.44: 24.47 +- 2.76), and restless leg syndrome p = 0006. Results of analysis in ADHD subtypes on the clinical and neuropsychological found significant differences in MMMSEC orientation sub-score p=0.016; language sub-score p = 0.029; and total score p = 0.027, FIQ p<0.001, SPPAHI score p=0048. Multivariate analysis found that parenting style p<0.001 (7.574 - 428.293), family income p<0.001 (10.359 -390.772), and nutritional history of BGM p = 0.029 (1.325 - 203.234), were independent risk factors for ADHD. Conclusions. 10R DAT1 polymorphism frequency were higher in Yogyakarta area than other countries, 7R DRD4 alleleic pattern was not found while the most common were 2R DRD4, 9/10R DAT1 polymorphism were significantly associated with VIQ score, whereas polymorphism gen DRD4 2R and DAT1 10R were not associated with AHD and also with the particular clinical and neuropsychological features, there were no differences in the proportion of 10R DAT1 allele and 2R DRD4 allele between ADHD subtypes and there were differences in the clinical and neuropsychological profiles between ADHD subtypesdifferences in the clinical and neuropsychological profiles between ADHD subtypes

Kata Kunci : ADHD, gen DRD4, gen DAT1, neurologi klinis, neuropsikologi, test fungsi kognitif, ADHD, DRD4 gene, DAT1 gene, clinical neurology, neuropsychology, cognitive function tests