Xiaocai Gao

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 (p = 0.02) and spatial localization (p = 0.03), but not with inhibition, shifting, updating, visuo-spatial working memory, long-term memory, and others (p > 0.05) 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.

Variations in 5-HT2A influence spatial cognitive abilities and working memory.

BACKGROUND 5-hydroxytryptamine receptor 2A (5-HT2A) participates in diverse psychiatric disorders by regulating the activity of serotonin. Some previous studies have also suggested that the receptor is involved in cognitive abilities of disease groups. We hypothesize that some functional genetic variants in 5-HT2A have certain specific influences on cognitive abilities in a normal population. METHOD To confirm this hypothesis, two polymorphisms (rs6313 and rs4941573) in 5-HT2A were selected, and a population-based study was performed in a young healthy Chinese Han cohort. RESULTS The results indicated that the rs6313 and rs4941573 were associated with touching blocks and mental rotation-3D error ratio in males, and the rs4941573 was associated with visuo-spatial working memory in the whole cohort. CONCLUSION All the findings suggest that 5-HT2A participates in human spatial cognitive abilities and spatial working memory.

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.

Possible Relationship between the COMT Gene Vel158Met Polymorphism and Psychometric IQ in Girls of the Qinba Region in China

Objective: Catechol-O-methyltransferase (COMT) gene was hypothesized to have a relationship with human prefrontal cortex (PFC) function and individual cognitive abilities. The object of this study was to investigate the possible impact of genotypes of COMT Val158Met polymorphism on cognitive ability among children living in the Qinba region in China. Method: A total of 305 children were included, 163 girls and 142 boys; both complete IQ evaluation and Val158Met genotyping results were obtained. The quantitative traits of psychometric IQ were calculated by using the Chinese Wechsler Intelligence Scale for Children. All subjects’ genotypes of COMT gene Val158Met polymorphism were identified with the restriction fragment length polymorphism method. Results: The F test showed that the average scores (including the Full Scale IQ, Verbal Scale IQ, Performance Scale IQ and three index scores) did not significantly differ among different groups defined by Val158Met genotypes, neither in boys nor in the total group (p > 0.05). There was a significant difference between the average of Freedom from Distractibility score among different genotypes found in girls (p = 0.033). Conclusion: Our results indicate that COMT gene Val158Met polymorphism may be related to the intelligence of Chinese girls, although the results cannot withstand multiple testing. Consequently, further studies with larger samples and perfect design still need place more emphasis on the gender difference and compensation effect of dopamine activity in PFC.

Association Analysis Between 12 Genetic Variants of Ten Genes and Personality Traits in a Young Chinese Han Population

Some genes involved in neurotransmission synthesis and transmission have been hypothesized to affect personality traits. To investigate the possible roles of these genes in personality traits of 16 Personality Factor Questionnaire, we performed a population-based study in a young Chinese Han cohort. In the study, we selected some functional variations in ten candidate genes (COMT, DBH, DRD2, DRD3, DAT, MAOA, GRM1, GRIN2B, 5-TH2A, and 5-TH6) encoding components in dopamine, glutamate, and 5-hydroxytryptamine pathways. The results showed the T102C in 5-TH2A was associated with X3 (emotional and quiet alertness) and B (reasoning) (F = 4.71 and 6.23; p = 0.009 and 0.002), Val158Met in COMT with E (dominance) (F = 7.01; p = 0.0009), while the variations in DBH, DRD2, DRD3, MAOA, GRM1, GRIN2B, and 5-TH6 were not associated with any of the personality traits. This finding suggests that T102C in 5-TH2A and Val158Met in COMT play roles in some human personality traits.

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.

Positive association of neuroligin-4 gene with nonspecific mental retardation in the Qinba Mountains Region of China.

Objective Neuroligin-4 is essential for proper brain function. Some studies indicate a close relationship between neuroligin-4 and several human psychiatric conditions. Methods The case–control method was used to study the association between nonspecific mental retardation (NSMR) and genetic variants of neuroligin-4 gene (NLGN4). Five single nucleotide polymorphisms (SNPs: rs5916271, rs7049300, rs6638575, rs3810686, and rs1882260) were genotyped by PCR-RFLP/SSCP method in the NLGN4. Results Individual SNP analysis shows significant differences at SNPs rs3810686 and rs1882260 for allele frequency when NSMR cases and controls [odds ratio (OR)=1.589, 95% confidence interval (CI)=1.035–2.438, χ2=4.53, df=1, P=0.033; OR=2.050, 95% CI=1.211–3.470, χ2=7.38, df=1, P=0.007, respectively] were compared. Further haplotype analysis indicates that there are two haplotype sets, rs3810686-rs1882260 and rs6638575-rs3810686-rs1882260, which show statistical differences between NSMR cases and controls (χ2=6.79, df=2, global P=0.034; χ2=9.29, df=2, global P=0.0096, respectively). Conclusion The results suggest a positive association between the genetic variants of the NLGN4 and NSMR in the Chinese children from Qinba Mountains Region.

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.

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.

Distribution of apolipoprotein E allele frequencies of the Han Chinese in an iodine-deficient mountainous area

Background: Iodine deficiency is common in the Qinba mountainous area and fetal iodine deficiency disorder (FIDD) is endemic. Our previous study demonstrated that apolipoprotein E (ApoE) was a genetic risk factor for FIDD in the local area. Aim: In order to achieve a better understanding of the aetiology of iodine deficiency-based mental retardation in the Qinba mountainous area, we conducted further studies of ApoE allele frequencies obtained from the local population. Subjects and methods: A total of 818 samples from four counties in the iodine-deficient area were recruited for the study of the ApoE genotype and allele frequencies using the PCR-RFLP method, and were subsequently confirmed by sequencing. Results: The frequencies of ϵ2, ϵ3 and ϵ4 alleles of Han Chinese in Qinba were 9.67%, 81.30% and 9.03%, respectively. Furthermore, no significant differences in the distribution of ApoE (either genotype or allele frequencies) between any two subgroups divided according to location, sex and age (p > 0.05) were found. Surprisingly, however, we found a significant difference in the genotype and allele frequencies between Qinba and Shanghai (genotype: χ2 = 14.91, p = 0.0096; allele: χ2 = 15.07, p = 0.0009). Conclusion: The currently documented allele frequencies of ApoE in the Han Chinese population living in the open areas of China do not represent the distribution in the isolated Qinba mountainous area. The higher level of ϵ2 and ϵ4 allele frequencies in the Han Chinese living in the isolated Qinba area arise by chance or may result from genetic adaptation to an environment characterized by malnutrition and iodine deficiency, which may also contribute to the high incidence of mental retardation in these regions.