Manovikas Kendra Rehabilitation and Research Institute

Symptomatic remediation from attention deficit hyperactivity disorder (ADHD)-associated traits is achieved by treatment with methylphenidate (MPH)/atomoxetine (ATX). We have analyzed the association of functional CYP2D6 variations, rs1065852, rs3892097, rs1135840, and rs1058164, with ADHD in the Indian subjects. Subjects were recruited following the Diagnostic and Statistical Manual for Mental Disorders. Trait scores were obtained from the Conner's Parents Rating Scale-Revised. After obtaining informed consent, blood was collected for DNA isolation, and genotyping was performed by PCR or TaqMan-based methods. Probands were treated with MPH or ATX based on age, symptoms, and drug availability. Treatment outcome was assessed using a structured questionnaire. Data obtained was analyzed to identify the association of CYP2D6 variations and the SLC6A3 rs28363170 with the treatment outcome. The frequency of rs1135840 "G" and rs1065852 "G" was higher in the male ADHD probands. Bias in parental transmission (p=0.007) and association with higher trait scores were observed for rs1065852 "A". Independent influence of rs1065852 on ADHD was also observed. Probands carrying rs1065852 'GG', rs1135840 'CG', and rs28363170 10R exhibited significant symptomatic improvement with MPH, while probands with rs1135840 'CC' and rs28363170 9R showed improvement after ATX treatment. ADHD probands having specific CYP2D6 genetic variations respond differentially to pharmaceutical intervention.

BackgroundIn different ethnic groups, birth related factors have shown significant influence in the etiology of Attention deficit hyperactivity disorder (ADHD). Based on these interesting findings, we aimed to investigate association between different pre- and post natal variables and ADHD associated traits in Indian subjects.MethodsADHD Probands recruited based on the DSM-IV, were assessed by the Conner’s Parent Rating Scale for behavioral problem (BPr), inattention (IA), hyperactivity (HA) and ADHD index (AI). Impulsivity (Imp) was assessed by the Tsukuyama scale.ResultsHigher paternal (Std β = 0.23) and lower maternal (Std β = 0.21) age showed significant association with Imp of the probands. Higher paternal age also revealed association with BPr (Std β = 0.18). Age of onset was distinctly associated with AI (Std β < 0.16) while developmental delay was negatively correlated with BPr, Imp, IA and birth weight (r < − 0.13); also confirmed by Posthoc-ANOVA (P < 0.05).ConclusionWe infer that parental age, developmental delay and birth related variables may have a cumulative effect on ADHD symptom severity.

Cortical neuronal migration and formation of filamentous actin cytoskeleton, needed for development, normal cell growth and differentiation, are regulated by the cyclin-dependent kinase 5 (Cdk5). Attention deficit hyperactivity disorder (ADHD) is associated with delayed maturation of the brain and hence we hypothesized that cdk5 may have a role in ADHD. Eight functional CDK5 gene variants were analyzed in 848 Indo-Caucasoid individuals including 217 families with ADHD probands and 250 healthy volunteers. Only three variants, rs2069454, rs2069456 and rs2069459, predicted to affect transcription, were found to be bimorphic. Significant difference in rs2069456 “AC” genotype frequency was noticed in the probands, more specifically in the males. Family based analysis revealed over transmission of rs2069454 “C” and rs2069456 “A” to the probands. Quantitative trait analysis exhibited association of haplotypes with inattention, domain specific impulsivity, and behavioral problem, though no significant contribution was noticed on the age of onset of ADHD. Gene variants also showed significant association with cognitive function and co-morbidity. Probands having rs2069459 “TT” showed betterment during follow up. It may be inferred from this pilot study that CDK5 may affect ADHD etiology, possibly by attenuating synaptic neurotransmission and could be a useful target for therapeutic intervention.

Trisomy of the 21st chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located in the 21st chromosome were genotyped to understand their role in DS. Genomic DNA of eastern Indian probands with DS (N= 132), their parents (N= 209) and ethnically matched controls (N= 149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses.ETS2rs461155 showed high heterozygosity in DS. Significantly lower frequency ofSIM2C-G haplotype (rs2073601-rs2073416) was noticed in individuals with DS (Pvalue = 0.01669) and their fathers (Pvalue = 0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (Pvalue = 0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 ‘A’ allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population.

BackgroundIn plants, proteases execute an important role in the overall process of protein turnover during seed development, germination and senescence. The limited knowledge on the proteolytic machinery that operates during seed development in coconut (Cocos nucifera L.) prompted us to search for proteases in the coconut endosperm.FindingsWe have identified and purified a coconut endosperm protease (CESP) to apparent homogeneity. CESP is a single polypeptide enzyme of approximate molecular mass of 68 kDa and possesses pH optimum of 8.5 for the hydrolysis of BAPNA. Studies relating to substrate specificity and pattern of inhibition by various protease inhibitors indicated that CESP is a serine protease with cleavage specificity to peptide bonds after arginine. Purified CESP was often autolysed to two polypeptides of 41.6 kDa (CESP1) and 26.7 kDa (CESP2) and is confirmed by immunochemistry. We have shown the expression of CESP in all varieties of coconut and in all stages of coconut endosperm development with maximum amount in fully matured coconut.ConclusionSince the involvement of proteases in the processing of pre-proteins and maintenance of intracellular protein levels in seeds are well known, we suspect this CESP might play an important role in the coconut endosperm development. However this need to be confirmed using further studies.

Sen, Barshaa; Sinha, Swagatab; Ahmed, Shabinae; Ghosh, Saurabhc; Gangopadhyay, Prasanta Kumard; Usha, Rajammaa Author Information

(w ww .m ed kn ow .co m) . P=0.018), while no signifi cant difference in maternal transmission was observed (χ2 =3.33, P=0.068). No difference in allelic frequencies was observed (χ2 =0.065, P=0.968) between DS mother (n=68; C=0.846, T=0.154) and control mother (n=59; C=0.839, T=0.161). An earlier report from Varanasi (25.33°N, 83°E),[4] a north-eastern state of India, had shown strong association of 677T with Indian DS patients and 677T allele was considered as a risk factor for DS contributed by either parent. However data obtained in our study, based on eastern Indian population, do not support the conclusions made by earlier investigators; allelic frequencies were not much different in parents of DS patients as compared to controls. Any preferential transmission of T allele was also not observed.