Kejin Zhang

Effect of BDNF Val66Met Polymorphism on Digital Working Memory and Spatial Localization in a Healthy Chinese Han Population

Cognitive abilities are complex human traits influenced by genetic factors. Brain-derived neurotrophic factor (BDNF), a unique polypeptide growth factor, has an influence on the differentiation and survival of neurons in the nervous system. A single-nucleotide polymorphism (rs6265) in the human gene, resulting in a valine to methionine substitution in the pro-BDNF protein, was thought to associate with psychiatric disorders and might play roles in the individual difference of cognitive abilities. However, the specific roles of the gene in cognition remain unclear. To investigate the relationships between the substitution and cognitive abilities, a healthy population-based study and the PCR-SSCP method were performed. The results showed the substitution was associated with digital working memory (pu2009=u20090.02) and spatial localization (pu2009=u20090.03), but not with inhibition, shifting, updating, visuo-spatial working memory, long-term memory, and others (pu2009>u20090.05) among the compared genotype groups analyzed by general linear model. On the other hand, the participants with BDNFGG had higher average performance in digital working memory and spatial localization than the ones with BDNFAA. The findings of the present work implied that the variation in BDNF might play positive roles in human digital working memory and spatial localization.

A study on the correlation between IL1RAPL1 and human cognitive ability

This study aimed to investigate the effects of IL1RAPL1 on the human cognitive ability. Four genetic marker sites, i.e., DXS1218, DXS9896, rs6526806 and rs12847959 on IL1RAPL1 were genotyped in 332 Qinba Mountain Area children. Meanwhile, a cognition test with a C-WISC scale was performed to study the relationship of genotype with cognition test scores. Results indicated that genotypes of DXS1218, DXS9896 and rs12847959 were associated with memory/concentration factor intelligence quotient (IQ) (P=0.027, 0.042, 0.029, respectively). DXS1218 also associated with full IQ, verbal IQ, and performance IQ (P=0.006, 0.014, 0.006, respectively). rs12847959 were related to verbal comprehension factor and perceptual organization factor IQ (P=0.021, 0.043, respectively). Further study on rat brain revealed that Il1rapl was mainly expressed in memory/concentration-associated encephalic regions, such as hippocampus, dentate fascia, osmesis perithelium, and piriform cortex. mRNA expression levels of Il1rapl in brains of rats with different learning and memory abilities showed significant difference. Combined data suggested that IL1RAPL1 affected human cognitive ability to some extent, especially the memory and concentration capability.

An Association Study on the Polymorphisms of Dopaminergic Genes with Working Memory in a Healthy Chinese Han Population

Working memory (WM) is a highly heritable cognitive trait that is involved in many higher-level cognitive functions. In the past few years, much evidence has indicated that the reduction of dopamine activity in human brain can impair the WM system of the neuropsychiatric disorders. In this study, we hypothesized that some genes in the dopamine system were involved in the individual difference of the cognitive ability in healthy population. To confirm this hypothesis, a population-based study was performed to examine the effects of COMT, DAT1, DRD1, DRD2, DRD3, and DRD4 on WM spans. Our results indicated there were significant associations of TaqIA and TaqIB in DRD2 with digital WM span, respectively (χ2xa0=xa09.460, pxa0=xa00.009; χ2xa0=xa06.845, pxa0=xa00.033). On the other hand, we found a significant interaction between Ser9Gly in DRD3 and TaqIA of DRD2 on digital WM span (Fxa0=xa03.207, pxa0=xa00.013). COMT, DAT1, DRD1, and DRD4, however, had no significant effects on digital and spatial WM spans (χ2<3.84, pxa0>xa00.05). These preliminary results further indicated that certain functional variants in dopamine system, such as TaqIA and TaqIB of DRD2, were possibly involved in difference of WM in a healthy population.

Genetic Variations in FTSJ1 Influence Cognitive Ability in Young Males in the Chinese Han Population

Human cognitive ability is a trait that is known to be significantly influenced by genetic factors. Previous linkage data provide evidence suggesting that gene FtsJ homolog 1 (Escherichia coli) is associated with mental retardation. The gene may have a relation to individual differences in cognitive ability because it is most critical for brain development. In the present research, three tag single-nucleotide polymorphism (SNPs) (rs2268954, rs2070991, and rs5905692) in FtsJ homolog 1 (E. coli) are selected and genotyped by the PCR-SSCP method. An analysis of variance is performed to determine the relationship between the SNPs and cognitive ability of the Chinese Han population of youth in Qinba mountain. There are significant correlations between the variance in FtsJ homolog 1 (E. coli) and general cognitive ability, verbal comprehension, and preceptual organization. These findings suggest that genetic variations in FtsJ homolog 1 (E. coli) possibly influence human cognitive ability.

Variants in COMT and DBH Influence on Response Inhibition Ability in Chinese Han Females

Catechol-O-methyltransferase (COMT) and dopamine-beta hydroxylase (DBH) are key enzymes to breakdown dopamine. Some previous studies have indicated that val158met in COMT and 19xa0bp insertion/deletion in 5′ flank of DBH are related to the performance of executive function. To further investigate the associations of the two genes with executive function, we performed a population-based study in a Chinese Han population. The results indicated that val158met in COMT and the 19xa0bp insertion/deletion of DBH were associated with the average reaction time of response inhibition in female group (Pxa0=xa00.01, Pxa0=xa00.03), respectively. Furthermore, there was a significant interaction of the two genes on the reaction time (Pxa0=xa00.006). This present study suggests that not only do COMT and DBH influence independently on response inhibition in females, but also exert a significant interaction on response inhibition.

Association Between a Functional COMT Polymorphism, Mental Retardation and Cognition in Qinba Area Children

Catechol-O-methyl transferase (COMT) plays an important role in the metabolism of neurotransmitters. Two alleles of the COMT gene as a result of a G/A transition in the exon 4 can lead to different COMT enzymatic activities. Much genetic research has revealed that this COMT functional polymorphism was related to human psychiatric disorders. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to discern the relationships among the functional polymorphism of COMT, mental retardation (MR), and general cognitive ability of children. The results of the case-control analysis showed that there was no association between the frequencies of genotypes of COMT and MR (chi2=0.776, P>0.05) or between the frequency of COMT alleles and MR (chi2=0.335, P>0.05). COMT polymorphism was found in children whose intelligence quotient (IQ) was above 55. In normal children (IQ> or =85), the frequencies of high-activity allele COMTH and the homozygote genotype COMTHH were 60.98% and 79.28%, respectively. Both were higher than those of the borderline group (46.67% and 70.67%, 0.10 > P>0.05). Therefore, the result of this study suggests that this functional polymorphism is not an important risk factor for MR, but the COMTHH genotype may have a positive effect on cognitive performance in normal children in the Qinba area.

Positive association of the FTSJ1 gene polymorphisms with nonsyndromic X-linked mental retardation in young Chinese male subjects.

AbstractTo investigate the possible genetic association of nonsyndromic X-linked mental retardation (NS-XLMR) with FTSJ1 gene polymorphisms, a case–control association study was performed focusing on the Chinese Han population in the Qinba mountain region. Three common single nucleotide polymorphisms (SNPs) (rs2268954, rs2070991, rs5905692) in the gene were selected and genotyped using the polymerase chain reaction single-strand confirmation polymorphism (PCR–SSCP) method. Pairwise linkage disequilibrium (LD) analysis showed that the three SNPs were in strong LD (all D > 0.8). There were significant differences between cases and controls in allele frequency distribution of rs2268954 (P = 0.036), rs2070991 (P = 0.043), and rs5905692 (P = 0.014) and in the distributions of common haplotypes combined by these SNPs (global P = 0.01236) in male subjects. In female subjects, however, no positive results were found. Our results suggest a positive association between the genetic variants of the FTSJ1 gene and NS-XLMR in young male subjects in the Chinese Han population in the Qinba region.

A Family-based Association Study of DIO2 and children mental retardation in the Qinba region of China

Deiodinase enzyme II (DIO2) has an important role in individuals’ thyroid hormones’ level, the development of central and peripheral nervous systems and characterized by mental retardation (MR). The DIO2 gene was genotyped by using five haplotype-tagging single-nucleotide polymorphisms (SNPs) in 157 Chinese MR high-density family pedigrees, including 452 nuclear families and >1460 persons. The single marker and haplotype analyses were performed by Family-based Association Tests (FBAT). Three SNPs had P-values <0.05 in at least one inherited model survived with the correction. Several haplotypes composed of these SNPs were also associated with MR. The in silico analyses identified that one of the SNPs, rs1388378, may be a functional SNP. However, further in vitro studies of this SNP should be considered in elucidating its effect on gene expression and the possible role in MR susceptibility.

No observable relationship between the 12 genes of nervous system and reasoning skill in a young Chinese Han population.

Reasoning skill is an advanced cognitive ability which is needed for drawing inferences from given information. It is well known that the ability depends on the neural network of the frontal and parietal brain regions. In this study, we hypothesized that some genes involved in neurotransmitter systems were related to reasoning skill. To confirm this hypothesis, we examined the effects of 13 genes (BDNF, NRSF, COMT, DBH, DRD2, DRD3, DAT1, MAOA, GRM1, GRIN2B, TPH2, 5-HT2A, and 5-HT6) in neurotransmitter systems on the non-verbal reasoning and verbal reasoning skills. The results indicated there were on significant effects of the 17 functional variants of these genes on the performance of non-verbal reasoning and verbal analogical reasoning skills (χ2xa0>xa03.84, dfxa0=xa01, Pxa0>xa00.05). This study suggests that some of the functional variations in BDNF, COMT, DBH, DRD2, DRD3, MAOA, 5-HT2A, 5-HT6, GRM1, and GRIN2B have no observable effects on the certain reasoning skills in a young healthy Chinese Han population.

Genetic Polymorphism of GABRR2 Modulates Individuals' General Cognitive Ability in Healthy Chinese Han People.

Previous studies have indicated that the cognitive impairment or deficit is associated with GABAergic signaling in central nervous system. Inspired by the finding that receptor GABRR2 modulates concentration of GABA and phasic inhibitory GABAergic transmission in brain. This study investigated to what extent a genetic variant (c.1423C>T, rs282129) of GABRR2 gene modulates individuals’ general cognitive ability in 987 Chinese Han people. Results showed a significant influence of GABRR2 gene polymorphism on individuals’ Raven’s Standard Progressive Matrices (RSPM) performance (Fxa0=xa03.58, Pxa0=xa0.028 by ANOVA and χ2xa0=xa09.35, Pxa0=xa0.009 by K–W test, respectively), even if non-genetic factors were partialed out (gender, major, types of birthplace, and socioeconomic index) (Bxa0=xa0−.67, SExa0=xa0.26, txa0=xa02.63, Pxa0=xa0.009). The finding provided a strong evidence, to our knowledge, for the view that genetic variant of GABRR2 gene may contribute to the difference of individuals’ general cognitive ability, independently.