Association of polymorphisms in the DCDC2 gene with developmental dyslexia in the Han Chinese

Background  Genetic association studies on populations of European origin have identified the DCDC2 gene as a susceptibility locus for developmental dyslexia. Here, we sought to investigate the association of DCDC2 polymorphisms with developmental dyslexia in children of Han Chinese origin.

Methods  We undertook a case-control genetic association study on 76 dyslexic children and 79 non-dyslexic matched controls. We isolated DNA from oral mucosal cell samples and genotyped two DCDC2 coding-sequence single nucleotide polymorphisms, rs2274305 and rs6456593, in each sample using SNaPshot single nucleotide extension. We compared the allele and genotype frequencies between the groups using the χ² test and analyzed the relationship between dyslexia and the polymorphism at both loci using unconditional logistic regression. We also predicted haplotypes and compared their frequencies between the two groups.

Results  The differences in the genotype distribution and the allelic genes of the two single nucleotide luci of the DCDC2 gene, rs2274305 and rs6456593, between the two dyslexic and non-dyslexic groups were statistically meaningless (P >0.05). The differences in the haplotype distributions of the DCDC2 gene between the dyslexic and normal group were statistically meaningless (P >0.05).

Conclusion  The DCDC2 gene may not be a susceptibility factor for developmental dyslexia among the Han Chinese. However, methodological issues may have prevented the detection of positive associations.

     

Association of genetic variations of the prostasin gene with essential hypertension in the Xinjiang Kazakh population

Background  Transgenic overexpression of human prostasin in rats disturbs salt balance and causes hypertension. We investigated whether genetic variations in prostasin were implicated in hypertension or related phenotypes in the Xinjiang Kazakh population.

Methods  We sequenced all exons and the promoter regions of the prostasin gene in 94 hypertensive individuals, and the genotype identification was performed by the TaqMan polymerase chain reaction method. Case-control studies were conducted in 938 Kazakh subjects.

Results  E342K and 2827G>A, which are novel variants, were successfully genotyped in the general Xinjiang Kazakh population with a sample size of 938 individuals (406 men and 532 women). Only one hypertensive patient was identified with the E342K mutation. No significant association was observed between 2827G>A and hypertension. However, quantitative traits of hypertensive intermediate phenotypes were significantly associated with the A allele; P=0.041 and 0.034 for body mass index (BMI) in the additive and recessive models, P=0.042 and 0.018 for OGTT-2h glucose in the additive and recessive models, P=0.031 for IRT-3h insulin in the recessive model, and P=0.038 for serum potassium in the dominant model.

Conclusions  This study does not provide evidence of a major role of prostasin variation in blood pressure modulation. However, association of prostasin polymorphisms with hypertension and metabolic effects can be observed in our population. Further investigation is warranted to clarify the relevance of prostasin polymorphisms to blood pressure regulation.

     

Interaction between maternal 5,10-methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene variants to increase the risk of fetal neural tube defects in a Shanxi Han population

Background  The 5,10-methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) are attractive candidates for screening for risk of neural tube defects (NTDs). The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China.     

Methods  Fifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses.

Results  There was a significant difference for MTHFR genotype distribution for one site (C677T) between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group (55.9% vs. 35.3%, P <0.05). A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype.

Conclusion  Genetic interaction between MTHFR and MS genes raises the probability of neural tube defects.

     

Association of common polymorphisms in the LRP6 gene with sporadic coronary artery disease in a Chinese population

Background  Genetic factors contribute to the development of coronary artery disease (CAD). Recently, a missense mutation in the low density lipoprotein receptor related protein 6 (LRP6) gene, encoding low density lipoprotein receptor related protein 6, has been implicated in an autosomal dominant form of early-onset CAD. The aim of this study was to determine whether the common variants in LRP6 are associated with sporadic CAD in Chinese.

Methods  A total of 766 CAD patients and 806 healthy controls were included in this study. The presence of angiographic CAD was determined by coronary angiographic analysis. Six signal nucleotide polymorphisms (SNPs) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique.

Results  A significant association was detected between rs11054731 in LRP6 intron 2 and CAD in our cohort (P=0.001). The CC genotype and C allele frequency in the case group were 52% and 72%. Using a dominant model of inheritance, the C allele of rs11054731 was shown to be an independent risk factor for CAD with an OR of 1.45 (95% CI: 1.19–1.77, P=0.0002). With the stratification according to the number of affected coronary arteries, an association was observed between rs11054731 and CAD (P=0.0002). No significant association was observed between any other SNPs and the risk of CAD.

Conclusion  The C allele of the rs11054731 within the LRP6 gene was associated with increased risk and extent of CAD in Chinese.

     

Rs548234 polymorphism at PRDM1-ATG5 region susceptible to rheumatoid arthritis in Caucasians is not associated with rheumatoid arthritis in Chinese Han population

Background  A previous study has shown that rs548234 polymorphism at PRDM1-ATG5 region is associated with rheumatoid arthritis (RA) in Caucasian populations. The aim of this study was to investigate the effect of rs548234 polymorphism at PRDM1-ATG5 region on susceptibility to RA in Chinese Han population.

Methods  We genotyped 848 RA patients and 1431 matched healthy controls for rs548234 single-nucleotide polymorphism (SNP) with a predesigned TaqMan SNP genotyping assay. Association analyses were performed on the whole data set and on rheumatoid factors (RF) and anti-cyclic citrullinated peptides (anti-CCP) antibody. Finally, we carried out combined analysis of rs548234 association with RA based on the published data.

Results  No significant difference in the genotype distribution between RA patients and healthy controls for rs548234 (C/T) polymorphism was found in Chinese Han population, neither in whole data set nor in stratified subsets, e.g. RF and anti-CCP status. Association analysis in different ethnic groups showed that rs548234 at PRDM1-ATG5 region was associated with RA in Caucasian ancestry but not in East Asian population.

Conclusions  Our results showed no involvement of rs548234 at PRDM1-ATG5 region in the susceptibility or clinical relevance of RA in Chinese Han population.

     

Relationship of plasminogen activator inhibitor 1 gene 4G/5G polymorphisms to hypertension in Korean women

Background  Hypertension (HTN) is a major determinant of various cardiovascular events. Plasma levels of plasminogen activator inhibitor 1 (PAI-1) modulate this risk. A deletion/insertion polymorphism within the PAI-1 loci (4G/4G, 4G/5G, 5G/5G) affects the expression of this gene. The present study investigated the association between PAI-1 loci polymorphisms and HTN in Korean women.

Methods  Korean women (n=1312) were enrolled in this study to evaluate the association between PAI-1 4G/5G gene polymorphisms and HTN as well as other metabolic risk factors. PAI-1 loci polymorphisms were investigated using polymerase chain reaction amplification and single-strand conformation polymorphism analysis.

Results  The three genotype groups differed with respect to systolic blood pressure (P=0.043), and diastolic blood pressure (P=0.009) but not with respect to age, body mass index, total cholesterol, low or high density lipoprotein cholesterol, triglycerides, or fasting blood glucose. Carriers of the PAI-1 4G allele had more hypertension significantly (PAI-1 4G/5G vs. PAI-1 5G/5G, P=0.032; PAI-1 4G/4G vs. PAI-1 5G/5G, P=0.034). When stratified according to PAI-1 4G/5G polymorphism, there was no significant difference in all metabolic parameters among PAI-1 genotype groups in patients with HTN as well as subjects with normal blood pressure. The estimated odds ratio of the 4G/4G genotype and 4G/5G for HTN was 1.7 (P=0.005), and 1.6 (P=0.015), respectively.

Conclusion  These findings might indicate that PAI-1 loci polymorphisms independently contribute to HTN and that gene-environmental interaction may be not associated in Korean women.

     

Polymorphism on chromosome 9p21.3 contributes to early-onset and severity of coronary artery disease in non-diabetic and type 2 diabetic patients

Background  Susceptibility to coronary artery disease (CAD) and diabetes is encoded by distinct, tightly-linked single nucleotide polymorphisms on chromosome 9p21. This study aimed to examine the association of variant rs1333049 on chromosome 9p21.3 with early-onset and severity of CAD in Chinese patients with and without type 2 diabetes, and to determine the possible impact of rs1333049 on glucose metabolism and inflammation pathways.

Methods  Genotyping of variant rs1333049 on chromosome 9p21.3 was performed in 2387 patients with and without diabetes who were undergoing coronary angiography to evaluate suspected or established CAD. Serum levels of glucose, glycosylated hemoglobin A_1c (HbA_1c), insulin, high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-6 were also measured, and compared with each patient’s genotype.

Results  The homozygous CC genotype of rs1333049 was significantly associated with CAD in diabetic (OR: 1.270, P=0.044) and non-diabetic (OR: 1.369, P=0.011) patients after adjusting for traditional risk factors. There was an association between CC genotype and number of diseased vessels in diabetics (P=0.019), but not in non-diabetics (P=0.126). Among diabetic patients, CC genotype carriers had an increased risk of early-onset CAD (OR: 2.367, P=0.008) and greater cumulative atherosclerotic burden compared with non-CC genotype carriers (Gensini score: 31.80±17.20 vs. 23.09±21.63, P=0.039). No significant differences were observed between genotypes of rs1333049 in serum levels of glucose, insulin, HbA_1c, or inflammatory cytokines for diabetic or non-diabetic patients with CAD.

Conclusions  This study demonstrated a significant association of rs1333049 polymorphism on chromosome 9p21.3 with CAD in Chinese diabetic and non-diabetic patients. The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and more severe CAD in diabetic patients through a novel biological pathway unrelated to glucose metabolism or inflammation.

     

Polymorphisms of dihydropyrimidine dehydrogenase gene and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population

Background  Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population.

Methods  Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment.

Results  The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c²=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c²=3.96, P=0.0465).

Conclusions  These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.

     

Effect of angiotensin converting enzyme gene I/D polymorphism in patients with metabolic syndrome in North Indian population

Background  Numerous studies have investigated the effect of angiotensin converting enzyme (ACE) gene I/D polymorphism and various cardiovascular risk factors in different populations with varied results. Currently, the association of ACE gene polymorphism with metabolic syndrome has not been studied in North Indians. While studies assessing the effect with polymorphism on each of the components of metabolic syndrome separately are present, data regarding the metabolic syndrome per se are sparse. The present study evaluated the effect of ACE gene I/D polymorphism in patients with metabolic syndrome in North Indian population at a tertiary care centre.

Methods  Fifty subjects, with thirty cases of metabolic syndrome (NCEP/ATP III guidelines, 2004) and twenty age and gender matched healthy controls were chosen. Detailed history was reviewed and clinical examination of the subjects was carried out. Relevant investigations including blood glucose (fasting and post prandial), blood urea, serum creatinine and serum lipids were done. DNA of cases and controls was analysed for I/D polymorphism using polymerase chain reaction.

Results  D/D genotype was more frequent in patients with metabolic syndrome as compared with healthy controls (P <0.05). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) was significantly higher in the D/D genotype than I/D and I/I genotypes (P <0.05). Our study also showed positive association between obesity, fasting blood glucose and ACE gene polymorphism while no association was found with triglycerides and high density lipoprotein cholesterol. The I/I group was significantly associated with waist circumference and fasting blood glucose (P <0.05).

Conclusion  Our study clearly showed that metabolic syndrome was associated with ACE gene polymorphism. However due to less number of subjects in the study further studies are needed to corroborate our results.

     

Functional polymorphism in exon 5 and variant haplotype of the interleukin-1 receptor-associated kinase 1 gene are associated with susceptibility to and severity of sepsis in the Chinese population

Background  The interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) is believed to play an important role in the pathogenesis of sepsis. Recent studies have suggested that the IRAK1 functional genetic variant could affect the severity of sepsis in Caucasians. In this report, we have investigated whether polymorphisms at the IRAK1 gene are associated with the susceptibility to and severity of sepsis among the Chinese population.

Methods  Haplotype-tagging single nucleotide polymorphisms (htSNPs) were selected from the HapMap database. They were genotyped in 255 patients with sepsis and 260 control subjects by PCR/restriction fragment length polymorphism (RFLP) analysis. The association between the selected htSNPs and the susceptibility to and severity of sepsis were estimated by Logistic regression with adjustments for age, sex, smoking, drinking, chronic disease status, Acute Physiology and Chronic Health Evaluation (APACHE) II score and primary diseases.

Results  rs1059702 was selected to represent the six linked htSNPs for IRAK1. Genotype frequencies of the htSNPs were in Hardy-Weinberg equilibrium for females, as were allele frequencies for both sex groups. Associations were observed in females between the htSNPs C/C genotype and increased susceptibility to sepsis (odds ratio (OR), 5.46; 95% confidence interval (CI), 1.12–26.67; P=0.018), and such associations were also observed between the IRAK1 variant haplotype (CC/C-allele) and increased susceptibility to sepsis (OR, 1.68; 95% CI, 1.05–2.70; P=0.031) when compared with the T/T + T/C genotype and the wild-type haplotype (TC + TT/T-allele). In the multiple organ dysfunction syndrome (MODS) subgroup, the variant haplotype was also associated with increased severity of sepsis (OR, 2.37; 95% CI, 1.13–4.94; P=0.02) when compared with the wild haplotype. This association was not significant in male patients.

Conclusions  The functional polymorphism in exon 5 and the variant haplotype of IRAK1 gene mediate susceptibility to and severity of sepsis. IRAK1 might be a genetic risk factor for the occurrence and development of sepsis in the Chinese population.

     

Proteomic analysis for detecting serum biomarkers related to smoking in humans

Background  Smoking is the leading cause of death in the world. This study focused on the difference of the serum proteomic profiling between healthy smokers and nonsmokers in order to find smoking-specific serum biomarkers.

Methods  Pattern-based proteomic profiling of 100 serum samples (from 50 Chinese male smokers and 50 matched nonsmokers) was performed through magnetic bead fractionation coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis (MALDI-TOF-MS) and resulting data were statistically analyzed by Ciphergen ProteinChip software 3.0.2.

Results  We found 72 serum peaks were significantly different between smokers and nonsmokers (P <0.05). Marker peaks of mass-to-charge ratio (m/z) 3159.13, 7561.03 and 9407.32 were smoking-specific.

Conclusion  The preliminary data suggested that smoking-specific serum biomarkers could be detected in humans.

     

Association of sterol regulatory element binding protein 2 and insulin-like growth factor binding protein 3 genetic polymorphisms with avascular necrosis of the femoral head

Background  Sterol regulatory element binding protein (SREBP)-2 plays a key role in lipid homeostasis by stimulating gene expression of cholesterol biosynthetic pathways. The insulin-like growth factor binding protein (IGFBP) family regulates growth and metabolism, especially bone cell metabolism, and correlates with osteonecrosis. However, association of their gene polymorphisms with risk of avascular necrosis of the femoral head (ANFH) has rarely been reported. We determined whether SREBP-2 and IGFBP-3 gene polymorphisms were associated with increased ANFH risk in the Chinese population.

Methods  Two single nucleotide polymorphisms of SREBP2 gene, rs2267439 and rs2267443, and one of IGFBP-3 gene, rs2453839, were selected and genotyped in 49 ANFH patients and 42 control individuals by direct sequencing assay.

Results  The frequencies of rs2267439 TT and rs2267443 GA of SREBP2 and rs2453839 TT and CT of IGFBP-3 in the ANFH group showed increased and decreased tendencies (against normal control group), respectively. Interaction analysis of genes revealed that the frequency of carrying rs2267439 TT and rs2267443 GA genotypes of SREBF-2 in ANFH patients was significantly higher than in the control group (P <0.05). Association analysis between polymorphisms and clinical phenotype demonstrated that the disease course in ANFH patients with the rs2453839 TT genotype of IGFBP-3 was significantly shorter than that of CT+CC carriers (P <0.01). CT+CC genotype frequency in patients with stage III/IV bilateral hip lesions was significantly higher than in those with stage III/IV unilateral lesions and stage II/III bilateral lesions (P <0.05–0.02).

Conclusions  Our results suggested that interaction of SREBP-2 gene polymorphisms and the relationship between the polymorphisms and clinical phenotype of IGFBP-3 were closely related to increased ANFH risk in the Chinese population. The most significant finding was that the CT+CC genotype carriers of IGFBP-3 rs2453839 were highly associated with the development of ANFH.

     

创伤骨科患者创伤严重程度和血浆D二聚体水平的相关分析

Background  The correlation between the plasma D-dimer level and deep vein thrombosis has not been conclusive in various studies. The aim of this research was to study the relationship between plasma D-dimer levels and the severity of orthopedic trauma by retrospective examination of orthopedic trauma cases.

Methods  Clinically acute trauma and non-acute trauma patients were selected and their plasma D-dimer levels were measured. Plasma D-dimer levels in patients of these two groups were compared. The relationship between the plasma D-dimer level and the severity of the trauma was also studied.

Results  There were 548 cases in the acute trauma group and 501 cases in the non-acute trauma group. The levels of plasma D-dimer were significantly higher in the acute trauma group than in the non-acute trauma group (P <0.01). In the acute trauma group, the correlation between the D-dimer level and the number of fractures was a positive linear correlation (r=0.9532).

Conclusions  Elevated plasma D-dimer is common in trauma patients. The D-dimer level and the number of fractures in the trauma patients are closely correlated. D-dimer is not only an indicator for the diagnosis of deep vein thrombosis and pulmonary embolus, but also an indicator of the severity of trauma in acute trauma patients.

     

Vitamin D receptor genetic polymorphisms and tuberculosis among Chinese Han ethnic group

Background  In epidemiological studies, tuberculosis (TB) appears intimately with vitamin D insufficiency whereas its relationship with vitamin D receptor (VDR) polymorphism caused by radical difference remains unspecified. This study aimed to investigate the relationship between vitamin D genetic polymorphism and tuberculosis in Han ethnic group.

Methods  Meta-analysis was adopted in the synthetic quantitative analysis of documents home and abroad on the relationship between vitamin D genetic polymorphisms and tuberculosis, which were openly published during June 2000 to January 2010. Random effect model and fixed effect model analyses were used to calculate the incorporated odds ratio (OR) based on the heterogeneity test data.

Results  A total of 6 eligible studies were included in this analysis. The FokI-ff genotype showed a significant marginal association (Fixed effect model: OR 1.91, 95% CI 1.44–2.52; Random effect model: OR 1.91, 95% CI 0.94–3.88), yet TaqI polymorphisms was not significantly related to TB.

Conclusion  The interaction between FoKI genotype polymorphism and TB observed demonstrates that vitamin D deficiency might exist as a risk factor during the development of TB in Han ethnic group and more evidences needed to validate the conclusion.

     

Mapping and localization of susceptible genes in asthma

Objective  To elucidate the development of mapping and localization of susceptible genes on chromosomes to asthma related phenotypes.

Data sources  Published articles about susceptibility genes for asthma related phenotypes were selected using PubMed.

Study selection  Using methods of candidate gene positional clone and genome-wide scan with linkage and association analysis to determine the location in the genome of susceptibility genes to asthma and asthma related phenotypes.

Results  There are multiple regions in the genome harboring susceptibility genes to asthma and asthma related phenotypes, including chromosomes 5, 11, 12, 6, 2, 3, 13, 7, 14, 9, 19 and 17. Many of these regions contain candidate genes involved in asthma development and progression. Some susceptible genes may affect the phenotype expression or response to therapy. In addition, the interaction of multiple genes with the environment may contribute to the susceptibility to asthma.

Conclusions  As an essential step toward cloning the susceptible genes to asthma, fine mapping and localization on chromosomes are definitely needed. Novel powerful tools for gene discovery and the integration of genetics, biology and bioinformatics should be pursued.

     

Expression of nucleophosmin in glandular epithelium of non-pregnant human endometrium during the menstrual cycle

Background  Nucleophosmin plays a critical role in embryonic development. This study aimed to examine the expression pattern of nucleophosmin in glandular epithelium of human endometrium during the menstrual cycle.

Methods  Endometrial tissues used for this study were obtained from 46 non-pregnant patients who underwent hysterectomy which had been performed to treat benign diseases. Nucleophosmin expression was assessed by in situ hybridization and immunohistochemistry.

Results  At the early-, mid- and late-proliferative phase, nucleophosmin mRNA was highly expressed in glandular epithelium of human endometrium. At the secretory phase, the expression of nucleophosmin mRNA was reduced in glandular epithelium in early-secretory phase, and the expression in mid- and late-secretory phases was not detected. Similarly, nucleophosmin protein was strongly expressed in endometrial glands throughout the proliferative phase, but was gradually reduced during secretory phase.

Conclusion  Nucleophosmin mRNA and protein are expressed in glandular epithelium of human endometrium throughout the menstrual cycle.

     

ROR2 gene is associated with risk of non-syndromic cleft palate in an Asian population

Background  The receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene has been recently shown to play important roles in palatal development in animal models and resides in the chromosomal region linked to non syndromic cleft lip with or without cleft palate in humans. The aim of this study was to investigate the possible association between ROR2 gene and non-syndromic oral clefts.

Methods  Here we tested 38 eligible single-nucleotide polymorphisms (SNPs) in ROR2 gene in 297 non-syndromic cleft lip with or without cleft palate and in 82 non-syndromic cleft palate case parent trios recruited from Asia and Maryland. Family Based Association Test was used to test for deviation from Mendelian inheritance. Plink software was used to test potential parent of origin effect. Possible maternally mediated in utero effects were assessed using the TRIad Multi-Marker approach under an assumption of mating symmetry in the population.

Results  Significant evidence of linkage and association was shown for 3 SNPs (rs7858435, rs10820914 and rs3905385) among 57 Asian non-syndromic cleft palate trios in Family Based Association Tests. P values for these 3 SNPs equaled to 0.000068, 0.000115 and 0.000464 respectively which were all less than the significance level (0.05/38=0.0013) adjusted by strict Bonferroni correction. Relevant odds ratios for the risk allele were 3.42 (1.80–6.50), 3.45 (1.75–6.67) and 2.94 (1.56–5.56), respectively. Statistical evidence of linkage and association was not shown for study groups other than non-syndromic cleft palate. Neither evidence for parent-of-origin nor maternal genotypic effect was shown for any of the ROR2 markers in our analysis for all study groups.

Conclusion  Our results provided evidence of linkage and association between the ROR2 gene and a gene controlling risk to non-syndromic cleft palate.

     

Use of the laser speckle flowgraphy in posterior fundus circulation research

Objective  To review articles aiming to present an overview of the principles, progress, uses and limitations of laser speckle flowgraphy (LSFG) in posterior fundus circulation research.

Data sources  The data used in this review was obtained mainly from the studies reported in PubMed using the key terms “laser speckle”, “ocular blood flowmetry” and “retinal imaging”.

Study selection  Relevant literatures on studies of LSFG were selected.

Results  LSFG is a unique, noninvasive imaging instrument to quantitatively visualize posterior fundus circulation in vivo. This review delineates the LSFG principles and development, demonstrates its extensive applicability for measurement of retina, choroid and optic nerve head circulation, compares it with other retinal imaging technologies and discusses unresolved issues.

Conclusions  LSFG is a noninvasive, two-dimensional objective diagnostic technique that has become a powerful method for the clinical and scientific assessment of posterior fundus circulation. Further studies may help to develop a more comprehensive evidence-based measurement and facilitate the correlation with other methods for chorioretinal circulation assessment.

     

Variants of tumor necrosis factor-induced protein 3 gene are associated with left ventricular hypertrophy in hypertensive patients

Background  Tumor necrosis factor-induced protein 3 (TNFAIP3) gene has been shown important in cardiac remodeling. The aim of the present study was to investigate whether the variants of TNFAIP3 gene are associated with left ventricular hypertrophy (LVH) in hypertensive patients.

Methods  Four representatives of all the other single nucleotide polymorphisms (SNPs) in TNFAIP3 gene were tested for association with hypertrophy in two independent hypertensive populations (n=2120 and n=324).

Results  We found that only the tag SNP (rs5029939) was consistently lower in the hypertensives with cardiac hypertrophy than in those without cardiac hypertrophy in the two study populations, indicating a protective effect on LVH (odds ratio (OR) (95% confidence interval (CI))0.58 (0.358–0.863), P=0.035; OR (95% CI)=0.477 (0.225–0.815), P <0.05, respectively). Multiple regression analyses confirmed that the patients with G allele of rs5029939 had less thickness in inter-ventricular septum, left ventricular posterior wall, relative wall thickness and left ventricular mass index than did those with CC allele in the hypertensive patients in both study populations (all P <0.01).

Conclusion  These findings indicate that the SNP (rs5029939) in the TNFAIP3 gene may serve as a novel protective genetic marker for the development of LVH in patients with hypertension.

     

A pilot study on the relationship between thyroid status and neuropsychiatric symptoms in patients with Alzheimer disease

Background  Growing evidence links alternation of the thyroid function to the pathogenesis and progression of Alzheimer disease (AD). However, only a few studies evaluate the association between thyroid hormone levels and neuropsychiatric manifestations in patients with AD. This study aimed to investigate the relationship of thyroid hormone levels and neuropsychiatric symptoms in euthyroid patients with AD.

Methods  Forty patients with AD (26 women and 14 men), with no prior AD treatment within 4 weeks before study entry, were evaluated on their thyroid status (total triiodothyronine (TT3), total thyroxine (TT4), and thyroid-stimulating hormone (TSH)), cognition (Mini-Mental State Examination (MMSE) and Alzheimer’s disease Assessment Scale-Cognitive Subscale (ADAS-cog)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)) and depression (Hamilton Rating Scale for Depression (HAMD₁₇)). The unique relationship between thyroid hormones and cognitive function and mood was examined with multivariate linear regression analyses. The thyroid status between the neuropsychiatric symptoms group and the non-neuropsychiatric symptoms group was examined with independent-samples t-test.

Results  In euthyroid AD patients with agitation and irritability has lower TSH serum level than those without these symptoms (t= –2.130, P <0.05; t= –2.657, P <0.05); and core score of HAMD is significantly associated with the serum level of TSH (β=0.395, P <0.01). There is no significant association between thyroid hormone levels and cognition (MMSE, ADAS-cog and its subscale score).

Conclusion  There might be a relationship between thyroid hormone levels and the neuropsychiatric symptoms in euthyroid patients with AD.