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Biomedical subjects

Lin He

Publications and source records attributed to Lin He.

At least 55 records · Page 3Linked to original sources
PubMed2006

A novel missense mutation of the EDA gene in a Mongolian family with congenital hypodontia.

X-linked hypohidrotic ectodermal dysplasia (HED) is a rare disease characterized by the hypoplasia or absence of eccrine glands, dry skin, scant hair, and dental abnormalities. Here, we report a Mongolian family with congenital absence of teeth inherited in an X-linked fashion. The affected members of the family did not show other HED characteristics, except hypodontia. We successfully mapped the affected locus to chromosome Xq12-q13.1, and then found a novel missense mutation, c.193C>G, in the ectodysplasin A (EDA) gene in all affected males and carrier females. The mutation causes arginine to be replaced by glycine in codon 65 (R65G) in the juxtamembrane region of EDA. In addition, 33% (3/9) of female carriers have a skewed X-chromosome inactivation pattern. Our result strongly suggests that the c.193C>G mutation is the disease-causing mutation in this family.

Anodontia↗
PubMed2006

Meta-analysis of association between ApoE epsilon4 allele and schizophrenia.

Several case-control studies have reported an association between schizophrenia and the epsilon4 allele of Apolipoprotein E gene. The results have been equivocal. This meta-analysis has evaluated the collective evidence for an association between the epsilon4 allele of Apolipoprotein E gene and schizophrenia. We analyzed published data sequentially first considering epsilon4 allele itself, and then epsilon4 carrier status as risk factors for schizophrenia using a sample of 17 population-based case-control studies, of which 6 were from Asian and 11 from Caucasian populations. The pooled odds ratios from the Caucasian populations showed a modest association with risk of schizophrenia for epsilon4 allele and epsilon4 carrier genotype. No other alleles or genotypes were significant in either Asian or Caucasian populations when analysed separately or combined, although the sample size had over 80% power to detect a significant odds ratio of 1.9 in Asian-population studies and 1.6 in Caucasian-population studies. After allowing for sensitivity analysis of the studies and assessment of publication bias, we conclude that the epsilon4 allele of Apolipoprotein E does not play a major role in risk of schizophrenia in Caucasian populations. Since significant heterogeneity was present among the 6 Asian populations reported to date, further studies using larger sample sizes are required.

Alleles↗
PubMed2006

Population-based and family-based association studies of an (AC)n dinucleotide repeat in alpha-7 nicotinic receptor subunit gene and schizophrenia.

The human alpha-7 neuronal nicotinic receptor subunit (CHRNA7) gene, located at chromosome 15q13.2, represents a strong candidate gene for schizophrenia. We have examined an (AC)n dinucleotide repeat in intron 2 of the CHRNA7 gene, which was previously shown to be strongly linked with schizophrenia, using both population-based and family-based association studies. In the population-based study, no significant differences between the genotype and allele frequency distributions in schizophrenia patients and control subjects were observed after correction for multiple testing, although a nominally significant association between the most common allele and schizophrenia was observed (P = 0.023, uncorrected for multiple testing). In the family-based study, there is no significant over-transmission (Transmitted/Non-transmitted: 61/50) of the same allele in 160 family trios. Overall, our results do not support a major role for the (AC)n dinucleotide repeat in schizophrenia susceptibility in Han Chinese. Further large-scale genetic studies based on a set of single nucleotide polymorphisms (SNPs) that fully characterize the linkage disequilibrium patterns at the CHRNA7 gene are necessary to determine the relevance of this gene as a risk factor for schizophrenia susceptibility.

Adult↗
PubMed2006

DNA-accelerated atom transfer radical polymerization on a gold surface.

A significantly increased polymer growth rate was observed during a surface-initiated ATRP reaction in the presence of DNA molecules. To investigate this phenomenon, thiolated single-stranded DNA molecules (ssDNAs) with ATRP initiators coupled at the distal point were used as the model molecule in the study. In comparison, a small molecule, HS-(CH(2))(11)NHCOC(CH(3))(2)Br, was used to provide a less-polar surface coating for polymer grafting. 2-Hydroxyethyl methacrylate (HEMA) and monomethoxy-capped oligo(ethylene glycol) methacrylate (OEGMA) were used as the ATRP monomers. The polymer growth rates were monitored by measuring the thickness of the polymer films formed at different times. Our results show that the presence of DNA molecules, although at a less-than-1% surface coverage, significantly accelerated the growth rates of both poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(oligoethylene glycol methacrylate) (POEGMA) at the beginning of the ATRP reactions. This accelerating effect was suspected to be a combined result of the highly charged sugar-phosphate backbones of DNA molecules and the formation of Cu complexes with DNA bases. After the initial polymer growth, a smaller yet constant polymer growth rate was observed, suggesting the reduced influence of DNA molecules as the ATRP reaction centers moved farther away from the surface. Similar to conventional ATRP reactions, the polymer growth from surface-anchored DNA molecules was found to be strongly dependent on the composition and the concentration of the catalysts used. Specifically, a catalyst mixture of CuCl/30% CuBr(2)/bpy with 23 mM CuCl was found to provide the optimal reaction condition to yield the fastest polymer film growth among the conditions tested.

Base Sequence↗
PubMed2006

Case-control association study of Disrupted-in-Schizophrenia-1 (DISC1) gene and schizophrenia in the Chinese population.

Disrupted-in-Schizophrenia-1 (DISC1) has first been identified as a candidate gene for schizophrenia through study of a Scottish family with a balanced (1; 11) (q42.1; q14.3) translocation. Lots of linkage and association studies supported DISC1 as a risk factor for schizophrenia. In this study, we genotyped three SNPs in DISC1 using a set of Han Chinese samples of 560 schizophrenics and 576 controls. No positive association was detected in the whole samples but analysis of allele frequencies in female samples showed weak association between SNP rs2295959 and the disease (chi(2)=6.188, P=0.0135, OR=0.728, 95% CI=0.567-0.935). Our results provide further evidence for sex difference for the effect of the gene on the aetiology of schizophrenia. Our findings also would encourage further studies, particularly family-based association studies with larger samples, to analyze the association between DISC1 and schizophrenia.

Adult↗
PubMed2006

Positive association between POU1F1 and mental retardation in young females in the Chinese Han population.

Genetic defects attributable to the genes involved in the hypothalamus-pituitary-thyroid (HPT) gland axis can cause abnormal thyroid hormone function and mental retardation (MR). Pit-1, encoded by the POU1F1 gene on human chromosome 3p11, is a pituitary-specific transcription factor responsible for the expression of several pituitary hormones. Thyrotropin is one of these hormones and is an important regulator in the HPT axis. One of the symptoms of patients with POU1F1 mutations is hypothyroidism and abnormalities of the nervous system early in the period after birth. We performed a case-control association study and a quantitative analysis of IQ to investigate the possible genetic contribution of POU1F1 in the Chinese Han population. Pairwise linkage disequilibrium (LD) analysis showed that rs300996, snp-7057 and rs300977 were in strong LD. There were significant differences of allele, genotype and haplotype frequencies of these three single nucleotide polymorphisms (SNPs) between cases and controls. When we conducted a breakdown comparison between cases and controls within different gender groups, no positive results in males were found. In females, however, we found significant differences between cases and controls in allele frequency distribution of rs300996 (P=0.0003), snp-7057 (P=0.0001) and rs300977 (P=0.0005) and in the distributions of common haplotypes combined by these SNPs (global P=0.0050). The P-value was 0.0301 for rs300996 and 0.0397 for the haplotype combination of rs300996-snp-7057-rs300977 in the analysis of the quantitative effects of the alleles and haplotypes on IQ in females. Our data suggest that POU1F1 may affect MR through a gender-specific mechanism.

Case-Control Studies↗
PubMed2006

A two-stage linkage analysis of Chinese schizophrenia pedigrees in 10 target chromosomes.

We performed a two-stage linkage scan involving 25 Chinese schizophrenia families, focusing on 10 target chromosomes which have already been the subject of considerable research. We initially genotyped 237 individuals with 186 markers, five candidate regions were then chosen for fine mapping and 49 additional markers were genotyped. In region 1q21-23, a maximum multipoint HLOD (HLOD=2.38) was observed between D1S484 and D1S2705, under the dominant model. In region 5q35, dominant HOLD of 2.36, 2.04, and 2.31 were found at marker D5S2030, D5S408, and D5S2006, respectively. Consistent multipoint results also supported linkage to this region under the same dominant model, with a highest HOLD of 2.47. Furthermore, single-point HLODs (HLOD=1.95 at D22S274, and HLOD=1.91 at D22S1157) were found in region 22q13, under the dominant model. Evidence from these three regions satisfied the criteria for suggestive linkage and should help in identifying schizophrenia susceptibility genes.

China↗
PubMed2006

Significant association between the genetic variations in the 5' end of the N-methyl-D-aspartate receptor subunit gene GRIN1 and schizophrenia.

BACKGROUND: N-methyl-D-aspartate (NMDA) receptors play important roles in many neurophysiological processes. Evidence from previous studies indicate that NMDA receptors contribute to the pathophysiology of schizophrenia. Two NMDA receptor subunit genes, GRIN1 and GRIN2A, are both good candidate genes for schizophrenia. METHOD: We genotyped five single nucleotide polymorphisms (SNPs) in GRIN1 and two in GRIN2A in 2455 Han Chinese subjects, including population- and family-based samples, and performed case-control and transmission disequilibrium test (TDT) analyses. A microsatellite in GRIN2A was genotyped in population-based samples and a Mann-Whitney U test was performed. RESULTS: A highly significant association was detected at the 5' end of GRIN1. Analyses of single variants and multiple-locus haplotypes indicate that the association is mainly generated by rs11146020 (case-control study: p = .0000013, odds ratio = .61, 95% confidence interval .50-.74; TDT: p = .0019, T/NT = 79/123). No association was found in the GRIN2A polymorphisms. CONCLUSIONS: Our results provide support for the hypothesis that NMDA receptors are an important factor in schizophrenia. Moreover, rs11146020 is located in 5' untranslated region where several functional elements have been found. Hence, the SNP is a potential candidate in altering risk for schizophrenia and worthy of further replication and functional study.

5' Flanking Region↗
PubMed2006

Further clarification of the contribution of the tryptophan hydroxylase (TPH) gene to suicidal behavior using systematic allelic and genotypic meta-analyses.

Suicide is a major public health issue, especially in western countries, accounting for approximately 1 million deaths every year throughout the world. The tryptophan hydroxylase (TPH) gene has been extensively studied as a candidate for suicidal behavior due to its role in serotonergic neurotransmission. Since the first study associating the gene with schizophrenia, there have been many attempts to replicate it. However, a number of these studies have produced contrary results, possibly reflecting inadequate statistical power and the use of different populations. Association data relating European and, more particularly, Asian populations has become increasingly available in recent years. To examine whether the aggregate data provide evidence of statistical significance, the current meta-analysis has combined all the published studies up to July 2005, and examined the polymorphisms (A779C, A218C, A-6526G) in the context of varied suicidal behaviors by analyzing the studies in total and in subsets. Compared with the inconsistent results of previous studies, the current results (22 references) confirm a strong overall association between suicidal behavior and the A779C/A218C polymorphisms, supporting the involvement of TPH in the pathogenesis of suicidal behavior.

Gene Frequency↗
PubMed2006

Procedures for a dynamical system on {0,1}n with DNA molecules.

In this paper, an improved form of DNA representations of elements in {0,1}n, which was first proposed by Fujiwara et al. [Fujiwara, A., Matsumoto, K., Chen, W., 2004. Procedures for logic and arithmetic operations with DNA molecules. Int. J. Found. Comput. Sci. 15, 461-474], is given. Using this improved representations, a procedure for cycling shift is proposed, and this procedure can be implemented in O(1) lab steps theoretically. Based on the operation for cycling shift, dynamic behavior of an operator on {0,1}n is investigated by DNA molecules.

Algorithms↗
PubMed2006

Association between the brain-derived neurotrophic factor (BDNF) gene and schizophrenia in the Chinese population.

Brain-derived neurotrophic factor (BDNF) belongs to a family of the neurotrophin which plays important roles in the development of the brain. BDNF has been suggested as a factor that increases the risk of schizophrenia. In this study, we genotyped three single nucleotide polymorphisms (SNPs) in the BDNF gene using a set sample of Han Chinese subjects consisting of 560 schizophrenes and 576 controls. No significant differences were found for either the genotype or allele distribution of analyzed polymorphisms, nor was any gender-specific association found. Thus, our data suggest that the BDNF gene may not be an important factor in susceptibility to schizophrenia.

Adult↗
PubMed2006

Association study of serotonin 2A receptor (5-HT2A) gene with schizophrenia and suicidal behavior using systematic meta-analysis.

Serotonin 2A receptor (5-HT2A) gene was implicated to be associated with both schizophrenia and suicidal behavior due to its role of key neurotransmitter in many physiologic processes. Association studies were reported in different populations, however, a great number of subsequent studies have produced contrary results, possibly reflecting inadequate statistical power. With the cumulative data in recent years in both European and Asian populations, particularly in Asian populations, it was necessary to carry out a comprehensive analysis of previous findings. The meta-analysis, therefore, combined all English and Chinese studies using multiple research methods published up to July 2005 to give a new picture of the role of the 5-HT2A gene. Compared with significant results reported previously, the current large samples (73 studies in all) failed to find significant association of the T102C polymorphism with either schizophrenia or suicidal behavior. Evidence of significant association was only detected between A-1438G and suicidal behavior. The current study did not support the association of the 5-HT2A gene with either schizophrenia or suicidal behavior.

Alleles↗
PubMed2006

Real-time three-dimensional echocardiography in assessment of congenital double orifice mitral valve.

The application of real-time three-dimensional echocardiography (RT 3DE) in the diagnosis of double orifice mitral valve (DOMV) was explored. Five cases of DOMV were examined by using 2-dimensional echocardiography (2DE) and RT 3DE. The spatial morphology of malformed mitral valve and its change in hemodynamics were observed. DOMV associated with partial atrioventricular septal defect was found in 3 cases (in which 2 cases had cleft mitral valve) and isolated DOMV in 2 cases; and moderate to severe mitral regurgitation was detected in 3 cases, and mild mitral regurgitation in 1, and no regurgitation in 1 case; 1 case had complicated rhumatic heart disease. Three cases were preoperatively discovered by 2DE, while 2 missed (1 case was discovered postoperatively). Four cases were diagnosed by RT 3DE preoperatively, and 1 case was diagnosed postoperatively (not examined by RT 3DE preoperatively). It was suggested that RT 3DE is a reliable technique in the diagnosis of DOMV; it permitted comprehensive and noninvasive assessment of mitral valve and may supplement 2D TTE in the assessment of DOMV.

Abnormalities, Multiple↗
PubMed2006

A novel deletion mutation in CCM1 gene (krit1) is detected in a Chinese family with cerebral cavernous malformations.

Cerebral Cavernous Malformations (CCM) are vascular malformations that are mostly located in the central nervous system (CNS) and occasionally within the skin and retina, which are classified into three types (CCM1, CCM2 and CCM3) by being located at different loci on chromosomes. At present, CCM1 (7q21), CCM2 (7p13-p15) and CCM3 (3q25.2-q27) are respectively linked to krit1 (Krev interaction trapped gene 1), MGC4607 and PDCD10 (programmed cell death 10). In this work, we identified a novel "GTA" deletion mutation at the acceptor splicing site of intron9/exon10 on krit1. The mutation results in an abnormally spliced protein by creating a premature termination code at the 23rd amino acid downstream from the sequence alteration. Our results are consistent with previous research on krit1 mutations and confirm the conclusion that KRIT1 haploinsufficiency may be the underlying mechanism of CCM1.

Adult↗
PubMed2006

Dysregulation of retinoid transporters expression in body fluids of schizophrenia patients.

This study aims to find the biomarkers or associated proteins in body fluids of schizophrenia patients so that we can further understand the etiology of schizophrenia. We applied proteomic technologies combining two-dimensional electrophoresis with Coomassie blue staining and mass spectrometry and identified a procedure for the clinical screening of disease-influenced body fluid proteins in two sets of samples, plasma from 19 schizophrenia patients and cerebrospinal fluid (CSF) from 35 drug-treated schizophrenic patients and 36 healthy controls. The expression of transthyretin (TTR) tetramer increased significantly in plasma of schizophrenic patients after a valid 2 months in-hospital antipsychotic treatment. Conversely, the expression of the TTR tetramer and apolipoprotein E (ApoE) was down-regulated by up to 1.68 and 3.62 times, respectively, in the CSF of schizophrenia patients compared to that of normal controls, which has not been reported previously. Considering that the TTR tetramer and ApoE are both retinoid transporters, retinoid dysfunction might be involved in the pathology of schizophrenia.

Adolescent↗
PubMed2006

A gene locus responsible for reticulate pigmented anomaly of the flexures maps to chromosome 17p13.3.

Reticulate pigmented anomaly of the flexures (RPAF), also called Dowling-Degos disease, is a rare autosomal-dominant cutaneous disorder characterized by spotted and reticulate pigmentation of the flexures. The gene, or even the chromosomal location, for RPAF has not yet been identified. In this study, one Chinese family with RPAF was identified and subjected to a genomewide screen for linkage analysis. We identified a locus at chromosome 17p13.3 with a maximum two-point limit of detection score of 3.61 at markers D17S831and D17S1866 (at recombination fraction theta=0.00). Haplotype analyses indicated that the disease gene is located within the 6.8 cM region distal to D17S1798. It is the first locus identified for RPAF. This study provides a map location for isolation of a disease gene causing RPAF.

Acanthosis Nigricans↗
PubMed2006

Administration of pioglitazone in low-density lipoprotein receptor-deficient mice inhibits lesion progression and matrix metalloproteinase expression in advanced atherosclerotic plaques.

Recent clinical trials have provided evidence that pioglitazone reduces cardiovascular events in patients with type 2 diabetes. However, the underlying mechanisms are not well understood. Because it has been well established that disruption of atherosclerotic plaques is a key event involved in acute myocardial infarction, we hypothesized that pioglitazone reduces cardiovascular events by stabilizing atherosclerotic lesions. In this study, we used an animal model to test our hypothesis. Low-density lipoprotein receptor-deficient (LDLR-/-) male mice were first fed a high-fat diet for 4 months to induce the formation of aortic atherosclerotic plaques and then treated with pioglitazone for the next 3 months. Analysis of atherosclerotic plaques at the end of the study showed that treatment with pioglitazone at 20 mg/kg/day reduced the progression of atherosclerotic plaques as compared to untreated mice. Furthermore, gene array analysis, quantitative real-time polymerase chain reaction, and immunohistochemical analysis showed that pioglitazone inhibited high-fat diet-induced upregulation of matrix metalloproteinase (MMP) expression. Finally, Sirius red staining showed that atherosclerotic lesions in mice receiving pioglitazone had higher collagen contents than those in untreated mice. This study demonstrated for the first time that administration of pioglitazone in LDLR-/- mice inhibited lesion progression and MMP expression in established atherosclerotic plaques and thus delineated a potential mechanism by which pioglitazone reduces cardiovascular events in patients with type 2 diabetes.

Animals↗