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OBJECTIVE@#Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation.@*METHODS@#We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotype-phenotype correlation analysis.@*RESULTS@#The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters.@*CONCLUSIONS@#The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Adaptor Proteins, Signal Transducing/genetics , Alleles , Asian People , Cardiomyopathy, Dilated/surgery , China/epidemiology , Defibrillators, Implantable , Exons , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , LIM Domain Proteins/genetics , Linkage Disequilibrium , Mutation , Polymorphism, Genetic , Sequence Analysis, DNAABSTRACT
Objective: Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation. Methods: We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotypephenotype correlation analysis. Results: The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters. Conclusions: The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.
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Huntington's disease (HD) is an autosomal dominant degenerative disease that mainly encompasses movement, cognition, and behavioral symptoms. The apolipoprotein E (APOE) gene is thought to be associated with many neurodegenerative diseases. Here, we enrolled a cohort of 223 unrelated Han Chinese patients with HD and 1241 unrelated healthy controls in Southeastern China and analyzed the correlation between APOE genotypes and HD phenotypes. The results showed that the frequency of the E4 allele (7.1%) in HD patients was statistically less than that in controls (12.0%) (P =0.004). In addition, we divided patients into motor-onset and non-motor-onset groups, and analyzed the relationship with APOE genotypes. The results, however, were negative. Furthermore, the age at onset (AAO), defined as the age at the onset of motor symptoms, was compared in each APOE genotype subgroup and multivariate regression analysis was used to exclude the interference of CAG repeat length on AAO, but no association was found between APOE genotypes and AAO. Finally, we analyzed adult-onset HD to exclude the interference caused by juvenile HD (n = 13), and the results were negative. Therefore, our study suggests that APOE may not be a genetic modifier for HD, especially for adult-onset HD among Chinese of Han ethnicity. To the best of our knowledge, this is the first study of the correlation between APOE genotypes and HD phenotypes in a Han Chinese population.
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Objective To investigate the association between rs11098403 of the NDST3 gene and schizophrenia among Han People in Yunnan. Methods A total of 364 Han patients with schizophrenia and 287 healthy Han people were enrolled in our study. SNaP shot was used to detect the genotype of rs11098403. Positive and Negative Symptoms scale (PANSS) was used to assess the symptoms of schizophrenia.Results No differences were found in the genotype and allele distributions of rs11098403 among patients and the control group (P＞0.05) . The allelic frequencies of rs11098403 showed no significant association with positive symptoms, negative symptoms or general symptoms (P＞0.05) . Conclusions Our study indicated that the association between NDST3 gene and schizophrenia might be specific to European population.
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Objective In order to study 275 reported height-associated single nucleotide polymorphisms (SNPs) in males of Northern Han Chinese. Methods Genotype information was detected by matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) in 266 Northern Han Chinese male samples. Using PLINK 1.09 and SPSS 19.0 software, three analysis methods were choosen, which were linear regression analysis, logistic regression analysis (tall ≥177.5cm, short ≤167.5cm), and logistic analysis (tall ≥180cm, short ≤165cm). Results We identified 16 SNPs significantly associated with height in our study group(P<0.05), which were analysised by linear regression analysis and logistic regression analysis. Of these, one had been previously described in East Asian (rs11170624), and six had been reported in European (rs10037512、rs17346452、rs2629046、rs7689420、rs8052560、rs7909670). The result of mean variance analysis suggested that the effect of rs11170624、rs17346452、rs7689420 and rs7909670 on height was consistent with previous study. However, compare with European population, the other three loci showed differential contribution of height variation in Northern Han Chinese. Conclusion Further statistical tests in larger numbers of individuals will be required to identify higher population specificity loci affecting stature of Han Chinese, and to build a height prediction model.
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Male infertility is a multifactorial syndrome encompassing a wide variety of disorders. In recent years, several genome-wide single-nucleotide polymorphism (SNP) association studies (GWAS) have been performed on azoospermia and/or oligozoospermia in different populations including two GWAS on nonobstructive azoospermia in China; however, the association of SNPs with idiopathic male infertility, especially asthenozoospermia and oligozoospermia, and their correlation with semen parameters are still not clear. To investigate genetic variants associated with idiopathic male infertility (asthenozoospermia, oligozoospermia, and oligoasthenozoospermia) in Chinese Han people, 20 candidate SNPs were selected from GWAS results and genotyped using the Sequenom MassARRAY assay. A total of 136 subfertile men and 456 healthy fertile men were recruited. rs6476866 in SLC1A1 (P = 1.919E-4, OR = 0.5905, 95% CI: 0.447-0.78) and rs10129954 in DPF3 (P = 0.0023, OR = 2.199, 95% CI: 1.311-3.689) were strongly associated with idiopathic male infertility. In addition, positive associations were observed between asthenozoospermia and rs215702 in LSM5 (P = 0.0016, OR = 1.479, 95% CI: 1.075-2.033) and between oligoasthenozoospermia and rs2477686 in PEX10 (P = 0.0011, OR = 2.935, 95% CI: 1.492-5.775). In addition, six SNPs (rs215702 in LSM5, rs6476866 in SLC1A1, rs10129954 in DPF3, rs1801133 in MTHFR, rs2477686 in PEX10, and rs10841496 in PED3A) were significantly correlated with semen quality alterations. Our results suggest that idiopathic male infertility in different ethnic groups may share the same mechanism or pathway. Cohort expansion and further mechanistic studies on the role of genetic factors that influence spermatogenesis and sperm progressive motility are suggested.
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Essential hypertension (EH) is affected by both genetic and environmental factors.The polymorphism of connexin (Cx) genes is found associated with the development of hypertension.However,the association of the polymorphism of Cxs with EH has not been investigated.This study aimed to investigate the association of the polymorphism of connexin (Cx) genes Cx37,Cx40,and Cx43 with EH in Kazak and Han Chinese in Xinjiang,China.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to analyze the polymorphism of Cx genes in Kazak and Han EH patients as well as their normotensive controls.The results showed that there were no significant differences in the frequencies of different three genotypes (A/A,A/G,and G/G) and A and G alleles of Cx40 rs35594137 and rs11552588 between EH patients and normotensive controis.However,in Kazak EH patients,the frequencies of three genotypes (A/A,A/G;and G/G) of Cx37 rs1630310 were 24.8％,47.2％ and 28.0％,respectively,which were significantly different from those in Han EH patients.In Han EH patients,the frequencies of the three genotypes (C/C,C/G and G/G) of Cx43 rs1925223 were 6.4％,35.6％ and 58.0％,respectively.Frequencies of the other four genotypes had no statistical differences among Kazak and Hart EH patients and their normotensive controls.These results suggest polymorphisms of Cx37 rs 1630310 and Cx43 rs 1925223 genes may be associated with the pathogenesis of EH.Carrying Cx37 rs1630310-A or Cx43 rs1925223-G genotypes may protect against the development of EH.
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?AIM: To study the association of the single nucleotide polymorphism ( SNP) rs1157699 in the calcitonin receptor-like receptor ( CRLR ) gene with primary angle closure ( PAC) in a Han Chinese population.?METHODS: All samples, involved 232 PAC cases and 306 controls, were obtained from an epidemiologic survey conducted in Funing, Jiangsu Province, China. Genotyping were carried out by TaqMan-MGB probe using the real time quantitative polymerase chain reaction system to study the relationship between SNP of rs1157699 in CRLR gene and PAC.?RESULTS: The prevalence of CRLRrs1157699 genotype was 67.4%, 30.0%, 2.6% for CC, CT, TT in cases, and 71.3%, 27.0%, 1.7% in controls respectively.There was no difference between the two groups in the distribution of genotype and allele frequencies of rs1157699 (P>0.05).?CONCLUSION:Our results do not support a significant role for rs1157699 in CRLR with PAC.
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Objective To study the clinical and genetic characteristics of keloid through investigating on four Han Chinese pedigrees.Methods The pedigree information and clinical data from Han Chinese keloid pedigrees were collected,which consisted of 22 patients in 127 family members,and then the charts of these pedigrees were constructed according to the data.Using the genetic model and pedigree analyses we summarized the clinical features of the disease in the families.Results Four Han Chinese keloid pedigrees were discovered.The three pedigree spans included 3 generations and one was 4 generations.Incidence of KD in the consanguinity family member was 23.7％ (23/93),and 20.8％ (11/53) in male KD,and 27.5％ (11/40) in female.Incidence of anterior chest KD was 40.9 ％.The inheritance pattern observed in these pedigrees was consistent with an autosomal dominant inheritance multi-gene hereditary disease with incomplete penetrance,and its nonpenetrance of KD gene carriers was 12％ (3/25).Conclusions The pattern of inheritance observed in these four Han Chinese keloid pedigrees is similar to previous reports and no gender differences are found in the incidence of disease,but differences in pathogenic site.Pedigree investigation helps to reveal the genetic characteristics of keloid.
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OBJECTIVE: We examined the demographic and clinical profiles of Parkinson's disease in Shanghai, China, to assist in disease management and provide comparative data on Parkinson's disease prevalence, phenotype, and progression among different regions and ethnic groups. METHODS: A door-to-door survey and follow-up clinical examinations identified 180 community-dwelling Han-Chinese Parkinson's disease patients (104 males, 76 females). RESULTS: The average age at onset was 65.16±9.60 years. The most common initial symptom was tremor (112 patients, 62.22%), followed by rigidity (38, 21.11%), bradykinesia (28, 15.56%) and tremor plus rigidity (2, 1.11%). Tremor as the initial symptom usually began in a single limb (83.04% of patients). The average duration from onset to mild Parkinson's disease (Hoehn-Yahr phase 1-2) was 52.74±45.64 months. Progression from mild to moderate/severe Parkinson's disease (phase≥3) was significantly slower (87.07±58.72 months; p<0.001), except for patients presenting initially with bradykinesia (53.83±24.49 months). Most patients (149/180, 82.78%) took levodopa with or without other drugs. The Hamilton Anxiety Scale revealed symptoms of clinical anxiety in 35 patients, and the Hamilton Depression Scale revealed depressive symptoms in 88 patients. The depressed or anxious subgroup (123 patients) demonstrated a significantly younger age at onset (55.54±7.68 years) compared with the overall mean (p<0.05). CONCLUSION: Unilateral limb tremor was the most common initial symptom, and motor function deteriorated slowly over ≅4−9 years. Earlier-onset patients experience greater psychiatric dysfunction. .
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Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Parkinson Disease/physiopathology , Age Factors , Age of Onset , Anxiety/epidemiology , Anxiety/physiopathology , China/epidemiology , Disease Progression , Depression/epidemiology , Depression/physiopathology , Epidemiologic Methods , Parkinson Disease/epidemiology , Parkinson Disease/pathology , Severity of Illness IndexABSTRACT
Background Vascular endothelial growth factor(VEGF) has been shown to be associated with the pathogenesis of age-related macular degeneration (AMD),therefore VEGF is a target for the treatment of wet AMD.However,the mechanism of VEGF in the pathogenesis of AMD is not clearly understood.Studying the correlation between VEGF gene polymorphism and AMD is becoming a new research hotspot,but relevant studies on Han Chinese have not been performed.Objective This study was to investigate the association between the VEGF +936C/T gene polymorphism and AMD in the Chinese population.Methods A pilot prospective and nonrandomized controlled trial was designed.This protocol complied with Declaration of Helsinki and was approved by the Ethic Committee of Chinese PLA Second Artillery General Hospital.Written informed consent was obtained from each subject prior to entering the study.Two hundred AMD patients and 200 age-and gender-matched normal controls were enrolled in this study.The genomic DNA was extracted from the peripheral blood samples of the subjects,and analysis of the VEGF polymorphisms at the +936 position in the promoter and 3＇-untranslated regions was performed by the restriction fragment length polymorphism method.Frequencies of the VEGF+936C/T genotype were compared between the two groups,and the risk of the VEGF+936C/T gene polymorphism in pre-disposing AMD was evaluated.Results No significant differences were seen in the incidence rates of smoking(P ＝ 0.76),hypertension(P ＝ 0.84),hyperlipidemia (P=0.71),diabetes mellitus (P=0.86) and cardiovascular disease(P=0.89) between the AMD group and the normal control group,and BMI was matched between the two groups (P =0.18).The prevalence of the TT genotype was 9.0％ (18/200)in the AMD group,but that in the normal control was 3.5％ (7/200),showing a significant difference between the two groups (P =0.03).The odds ratio (OR) was 2.73 with a 95％ confidence interval(CI) of 1.11 to 6.68 for AMD in this genotype.The CC and CT genotypes were not significantly different between the two groups (P =0.52,P =0.57).The genotype frequency and allele frequency conformed to HardyWeinberg equilibrium law.There were no significant differences found in the CC,CT,TT genotype frequencies among the early AMD,geographic atrophy AMD and choroidal neovascular AMD (all at P＞0.05).Conclusions The VEGF+936TT genotype is associated with AMD in Han Chinese population.
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AIM: To determine the distribution and frequency of functionally important allelic variants in the cytochromes P450 (CYP) 2C19, arylamine N-acetyltransferase 2 (NAT2), and thiopurine S-methyltransferase (TPMT) genes in the Han Chinese population and compare them with those of other ethnic populations.METHODS: Genotyping was carried out in a total of 210 unrelated Han Chinese volunteers derived from He-nan area. CYP2C19 variants ( * 2 and * 3), NAT2 variants ( * 6 and * 7), and TPMT variants ( * 3A, * 3B, and * 3C) were detected using polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP)assays. Detection of NA T2 * 5 and TPMT * 2 were performed using allele-specific polymerase chain reaction assays. RESULTS: Allele frequencies of CYP2C19 * 2 and * 3 occurred with 34.76 % and 6.4 %, respectively.Thirty-one persons ( 14.8 % ) carried two of these CYP2C19 alleles responsible for poor metabolizing activity.The frequencies of specif ic NAT2 alleles were 59.1%, 4.1%, 26.4 %, and 9.5 % for * 4 (wild-type), * 5(341C), * 6 (590A), and * 7 (857A), respectively. Genotyping of three different single nucleotide polymorphisms in the NA T2 gene revealed that the frequency of slow acetylators was 19.5 %. TPMT * 3C had an allelic frequency of 1.2 %. TPMT* 2, TPMT * 3A, or TPMT* 3B was not detected in the analysed samples. CONCLUSION: The overview of allele distribution for drug-metabolizing enzymes CYP2C19, NAT2, and TPMT among a Han Chinese population shows obvious difference to Caucasians. The data will be useful for clinical pharmacokinetic investigation and drug dosage administration to Han Chinese population.
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Aim The current study was conducted to investigate the effect of GSTP1 codon 105 polymorphism, alone and in combination with GSTM1-deletion polymorphism, on erythrocyte GST activity in 196 Han Chinese. Methods GST activity was measured in healthy Chinese by a spectrophotometric method (n=196;101 males and 95 females; age range 21～81 years; median 43.5 years). GSTM1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. Results The frequency of GSTM1 null genotype was 56.1% and the frequency of I/I, I/V, and V/V genotypes was 60.7%, 35.2% and 4.1%, respectively, in Han Chinese. The mean erythrocyte GST enzyme activity for I/V genotype group(3.53?0.63 U?g -1Hb) was significantly lower than that for I/I genotypes (4.25?1.07 U?g -1Hb, P=0.000), while significantly higher than that for V/V genotypes (2.44?0.67 U?g -1Hb, P=0.004). In GSTM1(-) group, the GST activity of carriers of GSTM1(-)/GSTP1- I/I is significantly higher than that of GSTM1(-)/GSTP1- I/V or-V/V, however, in GSTM1(+) group, there is no difference between different subgroups. There was no significant difference in the mean GST activity among different age groups. Erythrocyte GST activities were significantly higher in females than in males, but not significantly. Conclusion The GST activity measured by CDNB-based assay is probably strongly correlated with the GSTP1 105Val genotype, although other GST enzymes would tend to dilute the GSTP1 genotype effect.