Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and metastasis.Activin A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent ligands.AIM To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han population.METHODS In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were enrolled.Five SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction method.Hardy-Weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were conducted.RESULTS Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male smokers.In the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to ESCC.CONCLUSION ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

Role of matrix metalloproteinase,tissue inhibitor of metalloproteinase and tumor necrosis factor-α single nucleotide gene polymorphisms in inflammatory bowel disease

AIM:To study the (functional) relevance of single nucleotide polymorphisms (SNPs) in genes encoding matrix metalloproteinases (MMP)-1,-2,-3,-9,tissue inhibitors of metalloproteinases (TIMP)-1,-2 and tumor necrosis factor (TNF)-α in the etiopathogenesis of inflammatory bowel diseases (IBD),that may enhance susceptibility and/or disease severity. METHODS:Genomic DNA from 134 Crohn's disease (CD),111 ulcerative colitis (UC) patients and 248 control subjects was isolated from resected intestinal tissue or blood. Allelic composition at SNP loci was determined by PCR-RFLP or tetra primer ARMS PCR. RESULTS:The TIMP-1 genotype TT in women and T in men at SNP +372 T/C was found to increase CD susceptibility (39% vs 23.8%,P=0.018 and 67.9% vs 51.6%,P=0.055,respectively),while women with this genotype were less prone to development of fistulae during follow-up (41.4% vs 68.3%,P=0.025). Male IBD or CD patients carrying the TIMP-1 +372 T-allele expressed lower levels of TIMP-1 in surgically resected macroscopically inflamed tissue (0.065 < P < 0.01). The 5T5T genotype at MMP-3 SNP -1613 5T/6T increased the chance of stenotic complications in CD during follow-up (91.2% vs 71.8%,P = 0.022) but seemed to protect against colonic involvement of this disease at first endoscopic/radiologic examination (35.3% vs 59.5%,P=0.017). CONCLUSION:Allelic composition at the examinedSNPs in genes coding for TIMP-1 and MMP-3 affect CD susceptibility and/or phenotype,i.e.,fistulizing disease,stricture pathogenesis and first disease localisation. These findings reinforce the important role of these proteins in IBD.

Clinical significance of NOD2/CARD15 and Toll-like receptor 4 gene single nucleotide polymorphisms in inflammatory bowel disease

AIM： To evaluate the role of genetic factors in the pathogenesis of Crohn＇s disease （CD） and ulcerative colitis （UC）, we investigated the single nucleotide polymorphisms （SNPs） of NOD2/CARD15 （R702W, Gg08R and L1007finsC）, and Toll-like receptor 4 （TLR4） genes （D299G and T399I） in a selected inflammatory bowel disease （IBD） population coming from Southern Italy. METHODS： Allele and genotype frequencies of NOD2/ CARD15 （R702W, Gg08R and L1007finsC） and TLR4 （D299G and T399I） SNPs were examined in 133 CD patients, in 45 UC patients, and in 103 healthy controls. A genotype-phenotype correlation was performed. RESULTS： NOD2/CARD15 R702W mutation was significantly more frequent in CD （9.8%） than in controls （2.4%, P = 0.001） and in UC （2.3%, P = 0.03）. No significant difference was found between UC patients and control group （P 〉 0.05）. In CD and UC patients, no significant association with G908R variant was found. L1007finsC SNP showed an association with CD （9.8%） compared with controls （2.9%, P = 0.002） and UC patients （2.3%, P = 0.01）. Moreover, in CD patients, G908R and L1007finsC mutations were significantly associated with different phenotypes compared to CD wild-type patients. No association of IBD with the TLR4 SNPs was found in either cohort （allele frequencies： D299G-controls 3.9%, CD 3.7%, UC 3.4%, P 〉 0.05; T399I-controls 2.9%, CD 3.0%, UC 3.4%, P 〉 0.05）. CONCLUSION： These findings confirm that, in our IBD patients selected from Southern Italy, the NOD2/ CARD15, but not TLR4 SNPs, are associated with increased risk of CD.

Association of single nucleotide polymorphisms of brain-derived neurotrophic factor gene and multidrug resistance 1 gene to refractory epilepsy in Chinese Han children

BACKGROUND： There are two hypotheses for the underlying cause of refractory epilepsy： ＂target＂ and ＂transport＂. Studies have shown that brain-derived neurotrophic factor （BDNF） is over-expressed in refractory epilepsy. Multidrug resistance 1 （MDR1） gene encodes for P-glycoprotein, the primary ATP-binding cassette transporter in the human body. Some single nucleotide polymorphisms of the MDR1 gene have been associated with refractory epilepsy. OBJECTIVE： To investigate the association between BDNF gene C270T polymorphism and MDR1 T-129C polymorphism with refractory epilepsy in Chinese Han children through the use of polymerase chain reaction （PCR）-restriction fragment length polymorphism analysis. DESIGN, TIME AND SETTING： A case-control, genetic association study was performed at the Central Laboratory, Third Xiangya Hospital of Central South University from June 2005 to November 2007. PARTICIPANTS： A total of 84 cases of unrelated children with epilepsy, including 41 cases of refractory epilepsy and 43 cases of drug-responsive epilepsy, were enrolled. An additional 30 healthy, Chinese Han children, whose ages and gender matched the refractory epilepsy patients, were selected as normal controls. METHODS： Venous blood was collected and genomic DNA was extracted from the blood specimens. C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene were genotyped using PCR-restriction fragment length polymorphism analysis. Association analysis using the Ftest and Chi-square test was statistically performed between C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene and refractory epilepsy. MAIN OUTCOME MEASURES： The distribution of genotypes and allele frequencies of C270T polymorphism in BDNF gene and T-129C polymorphism in MDR1 gene. RESULTS： The distribution of CC, CT, and TT genotypes, as well as C and T allele frequencies, in the BDNF gene was not significantly different between the refractory epilepsy group, drug-responsive epilepsy group, or the normal control group （P 〉 0.05）. The distribution of TT genotype and T allele frequencies of the MDR1 gene was significantly different in the refractory epilepsy group compared with the drug-responsive epilepsy and normal control groups （P 〈 0.05）. Comparison of haplotype combinations demonstrated that there were no significant differences in combinations of TT＋CC, -FI-＋CT, TC＋CC, and TC＋CT among the three groups （P 〉 0.05）. CONCLUSION： C270T polymorphism of the BDNF gene was not associated with refractory epilepsy in Chinese Han children, but T-129C polymorphism in the MDR1 gene was associated with refractory epilepsy in Chinese Han children. The TT genotype and T allele frequencies could serve as susceptibility loci for refractory epilepsy. Interactions between C270T in BDNF gene and T-129C in MDR1 gene were not observed in refractory epilepsy in Chinese Han children.

Isolation,expression and single nucleotide polymorphisms(SNPs) analysis of LACCASE gene(LkLAC8) from Japanese larch(Larix kaempferi)

Nucleotide diversity (pi) and linkage disequilibrium (LD) analysis based on SNP marker could provide a sound basis for choosing an association analysis method. Japanese larch (Larix kaempferi) is an important timber coniferous tree species for pulping and papermaking, but its high lignin content has significantly restricted it application potential. In this study, the LACCASE gene, that plays an important regulatory role for lignin biosynthesis, was selected as research target. The full-length cDNA and genomic sequences of the encoding LkLAC8 gene were isolated from the LACCASE expressed sequence tags of the Japanese larch transcriptome database using the rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The cDNA was determined to be 1940 bp, with an open reading frame (ORF, 1734 bp) that encoded a protein of 577 AA. This protein contains four highly specific Cu2+ binding sites and 11 glycosylation sites, thus belonging to the LACCASE family. The deduced protein sequence shared an 89% identity with the PtaLAC from Pinus taeda. A real-time PCR analysis showed that the LkLAC8 transcript was expressed predominantly in mature xylem, with moderate levels in the immature xylem, cambium and mature leaves, the lowest in the roots. Lastly, the genomic sequences of LkLAC8 in 40 individuals from six naturally distributed populations of Japanese larch were amplified, and a total of 201 SNPs (103 and 98 mutation types of transition and transversion, respectively) were detected; the frequency of the SNPs was 1/19 bp. Nucleotide diversity among the six populations ranged from 0.0034 to 0.0053, which suggested that there were no significant differences among the populations. The LD analysis showed that the LD level decayed rapidly within the increasing length of the LkLAC8 gene. These results implied that LD mapping and association analysis based on candidate gene may be feasible for the marker-assisted breeding of new germplasms with low lignin in Japanese larch.

Relationship between Single Nucleotide Polymorphisms in -174G/C and -634C/G Promoter Region of Interleukin-6 and Prostate Cancer

The association between the single nucleotide polymorphisms （SNPs） in -174G/C and -634C/G of interleukin-6 （IL-6） promoter region and prostate cancer was examined in the population of Han people in Hubei region. TaqMan PCR was employed for the gene-typing of -174G/C and -634C/G in promoter region of IL-6 gene to compare the prostate cancer patients and normal controls in terms of genotype frequency, allele frequency and risk of prostate cancer. Enzyme-linked immu- nosorbent assay （ELISA） was used for the detection of IL-6 concentration in peripheral blood of the patients with prostate cancer and the relationship between the IL-6 level and the genotype was studied. Our results showed that in all the subjects, the genotype of genetic locus -174G/C was found to be GG and no CG and CC were observed. There was a significant difference in gene frequency of GG, CG and CC of -634C/G and allele frequency of G and C between prostate cancer patients and normal controls （P〈0.05） and the gene frequency of GG＋CG increased with the clinical stages and pathological grades of prostate cancer. The IL-6 level in GG＋CG group was significantly higher than that in CC group. It was concluded that no SNP in -174G/C IL-6 promoter region was found in the population of Han people in Hubei region. The SNP in -634C/G was, to some extent, associated with the development and progression of prostate cancer. The population with GG＋CG genetype has higher risk for prostate cancer.

Identifying changes in punitive transcriptional factor binding sites from regulatory single nucleotide polymorphisms that are significantly associated with disease or sickness

AIM To identify punitive transcriptional factor binding sites(TFBS) from regulatory single nucleotide polymorphisms(rS NPs) that are significantly associated with disease.METHODS The genome-wide association studies have provided us with nearly 6500 disease or trait-predisposing SNPs where 93% are located within non-coding regions such as gene regulatory or intergenic areas of the genome. In the regulatory region of a gene, a SNP can change the DNA sequence of a transcriptional factor(TF) motif and in turn may affect the process of gene regulation. SNP changes that affect gene expression and impact gene regulatory sequences such as promoters, enhancers, and silencers are known as rS NPs. Computational tools can be used to identify unique punitive TFBS created by rS NPs that are associated with disease or sickness. Computational analysis was used to identify punitive TFBS generated by the alleles of these rS NPs.RESULTS r SNPs within nine genes that have been significantly associated with disease or sickness were used to illustrate the tremendous diversity of punitive unique TFBS that can be generated by their alleles. The genes studied are the adrenergic, beta, receptor kinase 1, the v-akt murine thymoma viral oncogene homolog 3, the activating transcription factor 3, the type 2 demodkinase gene, the endothetal Per-Arnt-Sim domain protein 1, the lysosomal acid lipase A, the signal Transducer and Activator of Transcription 4, the thromboxane A2 receptor and the vascular endothelial growth factor A. From this sampling of SNPs among the nine genes, there are 73 potential unique TFBS generated by the common alleles comparedto 124 generated by the minor alleles indicating the tremendous diversity of potential TFs that are capable of regulating these genes.CONCLUSION From the diversity of unique punitive binding sites for TFs, it was found that some TFs play a role in the disease or sickness being studied.

Assessment of single nucleotide polymorphisms associated with steroid-induced ocular hypertension

AIM:To access the association of forty-eight single nucleotide polymorphisms(SNPs)identified from Caucasian population with steroid-induced ocular hypertension(OHT)in India population.METHODS:Fifty-four triamcinolone-acetonide(TA)and for ty-seven dexamethasone(Dex)administered subjects were enrolled in the study after a written consent.Intraocular pressure(IOP)values were recorded for a period of 6-month post steroid injections and patients were grouped as steroid-responders(SR:IOP≥21 mm Hg)and non-responders(NR:IOP≤20 mm Hg).Genomic DNA was isolated from peripheral venous blood.Forty-eight SNPs identified in TA treated Caucasian patients by genome wide association study(GWAS)were genotyped using iPLEXTM MassA RRAY among TA as well as Dex administered Indian patients.Genotyping data of 48 general subjects from a previous study were considered as reference controls for statistical analysis.Genotypic frequencies were calculated and P-value,Chi-square and odds ratio at 95%confidenceinterval of group A(steroid treated vs controls),group B(SR vs NR),group C(phenotype correlation:influence of time,severity and gender on IOP rise),were calculated.P<0.05 was considered to be statistically significant.RESULTS:OHT was observed in 50%of TA and 26%of Dex administered patients,respectively.IOP rise was mostly severe(>30 mm Hg)and immediate(<1 wk)among TA-SR patients while it was noticed to be mild(<30 mm Hg)and between 1-2 mo among Dex-SR patients.Logistic regression for risk factor correlation with OHT remained non-significant,hence these factors were not considered as confounding parameters for further analysis.rs133,rs34016742,rs274554,rs10936746,rs274547,rs804854,rs7751500,rs359498,and rs7547448 SNPs significantly varied even after Bonferroni corrections(P<0.0025;group A).rs1879370(TA)and rs6559662(Dex)were significantly(P<0.05)associated with OHT(group B).rs133(severe IOP rise),rs11047639 and rs1879370(male gender),and rs11171569(immediate IOP rise)significantly(P<0.05)influenced the phenotype correlation only among TAOHT patients.However,the significance of these SNPs in group B and phenotype analysis(group C)was lost upon Bonferroni corrections(P<0.0025).CONCLUSION:Prevalence of OHT in study population is observed to be similar to other studies both in TA and Dex treated patients.We can correlate rs34016742 involved in diabetes signaling pathway to the occurrence of ocular edematous and inflammatory conditions.Except rs133 that is involved in neuro-degeneration and myopia occurrence,none of the other SNPs identified in Caucasian population possess any correlation with OHT incidence in TA and Dex administered Indian subjects.

Association of eleven single nucleotide polymorphisms with refractive disorders from Eskisehir,Turkey

AIM:To investigate relationship between refractive errors and eleven single nucleotide polymorphisms(SNPs)in HGF,GC,MFN1,GNB4,and VDR genes in Turkish population.METHODS:A group of 212 participants with myopia(n=91),hyperopia(n=45),and emmetropia(n=76)were investigated in this study.SNPs in HGF,GC,MFN1,GNB4 and VDR genes were studied by Snap Shot technique.RESULTS:The patients in this study consists of 47 female/44 male(age:23.47±4.30)patients with myopia,20 female/25 male(age:31.20±8.02)with hyperopia and 33 female/43 male(age:25.22±6.60)with emmetropia.The genotype distribution of the rs7618348 polymorphism,which was the only statistically significant one between myopia and emmetropia group.The genotype distribution of the rs3819545,rs3735520,rs7041,and rs2239182 polymorphisms,which were statistically significant between hyperopia and emmetropia groups.CONCLUSION:The importance of genetic predisposition to refractive errors with respect to etiology of the disease is revealed.It is known that polymorphism studies may differ because of genetic diversity among populations so larger cohort studies are required in different populations to enlighten the etiology of the refractive errors.

Association of Single Nucleotide Polymorphisms in IRF6 and TGFA Genes With Nonsyndromic Cleft Lip With Or Without Cleft Palate in Chinese Patients

Objective： Nonsyndromic cleft lip with or without cleft palate（NSCL/P） is a common birth defect with unclear etiology. Both genetic and environmental factors may contribute to NSCL/P. Many genes have been identified as candidate genes associated with this disease. Interferon regulatory factor 6（IRF6） gene and transforming growth factor-a（TGFA） gene seem to be crucial in the predisposition of NSCL/ P. Here we evaluated some single nucleotide polymorphisms（SNPs） loci of TGFA and IRF6 genes in Chinese nuclear families consisting of fathers, mothers and affected offspring with NSCL/P. Methods：Fifty patients of NSCL/P were confirmed by the plastic surgeons. They and their parents were included in the study, all with the informed consents. SNPs loci of TGFA and IRF6 genes were analyzed by microarray technology. Some PCR products were randomly chosen and sequenced to check microarray results. The distribution of gene type and allele frequency between patient group and parents group were compared. Then a Haplotype Relative Risk（HRR） and Transmission Disequilibrium Test（TDT） were performed. Results：The sequences of randomly selected PCR products were all consistent with the microarray results. All loci were in Hardy-Weinberg equilibrium. There were no significant differences in the distribution of genotypes and alleles between patients and their parents. Using HRR and TDT analyses the V274I of IRF6 was associated with NSCL/P, while another SNP locus oflRF6 was not. Strong evidence of linkage disequilibrium was found between the 2 SNP loci of TGFA and disease with the HRR analysis, but not with the TDT analysis. Conclusion：Our study confirms the contribution of IRF6 in the etiology of NSCL/P in populations of Asian ancestry. The association of TGFA with NSCL/P requires further research.

Advances in Single Nucleotide Polymorphisms of Vitamin D Metabolic Pathway Genes and Respiratory Diseases

Vitamin D is a fat-soluble vitamin.It is an essential vitamin for human body.It has a classical effect on regulating calcium and phosphorus metabolism.Participate in cellular and humoral immune processes by regulating the growth,differentiation and metabolism of immune cells.A large number of studies in recent years have shown that vitamin D deficiency increases the incidence of respiratory diseases.Respiratory diseases mainly include bronchial asthma,chronic obstructive pulmonary disease,tuberculosis,acute upper respiratory tract infection and pneumonia.Vitamin D metabolic pathway genes play a very important regulatory role in the transformation of vitamin D into active vitamin D,including CYP2R1,CYP27B1,CYP24A1,VDBP,VDR five genes.Genetic polymorphism of genes is the molecular basis of individual differences and disease development.Therefore,this paper summarizes the research on single nucleotide polymorphism of vitamin D metabolic pathway gene and respiratory diseases.In order to provide a new idea for future treatment.

Gene-gene,gene-environment,gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,oxidative stress and beta cell apoptosis in T2 DM.Among the recognized markers are interleukin(IL)-6,IL-1,IL-10,IL-18,tissue necrosis factor-alpha(TNF-α),C-reactive protein,resistin,adiponectin,tissue plasminogen activator,fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance.Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatory cytokines have been reported as a risk for T2 DM.Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups.The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions.This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6,TNF-α,resistin and adiponectin in pathogenesis of T2 DM.

Association of three single nucleotide polymorphisms of ESR1 with breast cancer susceptibility:a meta-analysis

Expression of estrogen receptors is correlated with breast cancer risk,but inconsistent results have been reported.To clarify potential estrogen receptor（ESR）-related breast cancer risk,we analyzed genetic variants of ESR1 in association with breast cancer susceptibility.We performed a meta-analysis to investigate the association between rs2234693,rs1801132,and rs2046210（single nucleotide polymorphisms of ESR1）,and breast cancer risk.Our analysis included 44 case-control studies.For rs2234693,the CC genotype had a higher risk of breast cancer compared to the TT or CT genotype.For rs2046210,the AA,GA,or GA ＋ GG genotype had a much higher risk compared to the GG genotype.No significant association was found for the rs 1801132 polymorphism with breast cancer risk.This meta-analysis demonstrates association between the rs2234693 and rs2046210 polymorphisms of ESR1 and breast cancer risk.The correlation strength between rs2234693 and breast cancer susceptibility differs in subgroup assessment by ethnicity.

Tagging single nucleotide polymorphisms in the PPAR-γ and RXR-α gene and type 2 diabetes risk:a case-control study of a Chinese Han population

Peroxisome proliferator-activated receptor （PPAR-γ）,which is mainly involved in adipocyte differentiation, has been suggested to play an important role in the pathogenesis of insulin resistance and atherosclerosis. We investigated the frequencies of two common tagging polymorphisms of the PPAR-γ gene and two of PPAR-α with minor allele frequency （MAF）≥ 0.05 in the Chinese Han population and analyzed the correlation between the different genotypes and the risk of type 2 diabetes mellitus （T2DM）. TaqMan assay was performed to test the genotypes in T2DM patients （n = 1,105） and normal controls （n = 1,107）. Serum adiponectin concentration was measured by ELISA kit. The variant genotypes rs17817276GG, rs3856806CT and rs3856806CT/TT of PPAR-γ were associated with T2DM, P = 0.023,0.037 and 0.018, respectively. Furthermore, the prevalence of haplotype GT in PPAR-γ was less frequent in the case subjects （0.3%） than in the controls （1.9%） [P 0.001,OR（95%CI）=0.13 （0.06-0.31）]. Patients with genotype TT of rs3856806 had a higher serum level of adiponectin than those with the genotype CC and CT （P = 0.031 and 0.038, respectively）. There was no statistically significant difference between patients and controls in genotype distribution of rs6537944 and rs1045570 of the RXR-α gene. The present study suggests that the variant genotypes in the PPAR-γ gene could decrease the risk for the development of T2DM in the Chinese Han population.

Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population

In European populations,7 single nucleotide polymorphisms(SNPs) on chromosome 17q,3 SNPs on 17q12,and 4 SNPs on 17q24.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study.In Japanese populations,the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment.However,whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown.Therefore,we conducted a case-control study in a northern Chinese population and tested 2 SNPs,rs4430796 and rs1859962,on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve(PCR-HRM) combined with sequencing.We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients' lifestyles,onset ages,Gleason scores,PSA levels,and pathologic stages.We found a significant difference in the G allele of SNP rs1859962(P = 0.035,OR = 1.51,95% CI = 1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls(P > 0.05).Neither of the SNPs was significantly associated with the onset age,Gleason score,PSA level,pathologic stage,or other clinical indicators of patients with prostate cancer(P > 0.05).Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.

Preliminary study of single nucleotide polymorphisms of PRPS2 gene in overproducing type of gouty patients

目的 :探讨编码人磷酸核糖焦磷酸合成酶亚单位 2的基因 PRPS2单核苷酸多态性与产生过剩型痛风患者的关系。方法 :利用聚合酶链反应扩增健康人和产生过剩型痛风患者 PRPS2基因全部外显 (包括外显子与内含子交界区 )的片段 ,采用多荧光标记的 PCR单链构象多态性分析技术对扩增的片段进行了筛选 ,对筛选到的片段进行序列测定 ,并与正常序列进行对照分析。结果 :在 PRPS2基因的第一个外显子区发现了一个 SNP( exon1+45A/G) ,第六个内含子区发现了一个 SNP ( intron6+12G/A) ,健康人与患者间的频率比较分别为 P =0 .0 96和 P =0 .2 73。结论 :提供了 PRPS2基因 SNP的数据库信息 ,为研究痛风发病机制提供了新的途径。

Analysis of single nucleotide polymorphisms in the region of CLDN2-MORC4 in relation to inflammatory bowel disease

AIM:To investigate a possible genetic influence of claudin(CLDN)1,CLDN2 and CLDN4 in the etiology of inflammatory bowel disease.METHODS:Allelic association between genetic regions of CLDN1,CLDN2 or CLDN4 and patients with inflammatory bowel disease,Crohn's disease(CD)or ulcerative colitis were investigated using both a casecontrol study approach(one case randomly selected from each of 191 Swedish inflammatory bowel disease families and 333 controls)and a family-based study(463 non-Swedish European inflammatory bowel disease-families).A nonsynonymous coding single nucleotide polymorphism in MORC4,located on the same linkage block as CLDN2,was investigated for association,as were two novel CLDN2 single nucleotide polymorphism markers,identified by resequencing.RESULTS:A single nucleotide polymorphism marker(rs12014762)located in the genetic region of CLDN2 was significantly associated to CD(case-control allelic OR = 1.98,95%CI:1.17-3.35,P = 0.007).MORC4 was present on the same linkage block as this CD marker.Using the case-control approach,a significant association(case control allelic OR = 1.61,95%CI:1.08-2.41,P = 0.018)was found between CD and a nonsynonymous coding single nucleotide polymorphism(rs6622126)in MORC4.The association between the CLDN2 marker and CD was not replicated in the familybased study.Ulcerative colitis was not associated to any of the single nucleotide polymorphism markers.CONCLUSION:These findings suggest that a variant of the CLDN2-MORC4 region predisposes to CD in a Swedish population.

Corelation Between Single Nucleotide Polymorphisms in Mu Opioid Receptor Exon 2 and Stereotypic Behaviour in Sows

Three breeds of sows were observed to investigate the relationship between Single Nucleotide Polymorphisms（SNPs） in Mu Opioid Receptor（MOR）and stereotypic behaviour,such as,sham-chewing,bar biting and standing still in order to better understand the mechanism of stereotypic development of the animals in restrained conditions.MOR exon 2 partial sequences were amplified to analyze single nucleotide polymorphisms by PCR-SSCP.One SNP,a silence mutant was found.A significant difference （P〈0.01）was found in the frequency of genotypes in these 3 breeds where only the BB genotype,which was identical to that published in GenBank,was found in the Duroc breed,while no AA genotype was found in Landrace,3 genotypes AA,BB and AB were found in Yorkshire.The result also indicated that the individuals with AA and AB genotypes tended to be more active in sham-chewing than those with the BB genotype（P〈0.05）.The overall results of this study suggested that sham-chewing of sows may be subjected to both genetic control and environmental conditions,but activity level was more likely to be affected by their environment.We can putatively draw the conclusion that MOR gene has effect on the sham-chewing behavioral traits of sow.

Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.

Identification of Single Nucleotide Polymorphisms and Analysis of Linkage Disequilibrium in Different Bamboo Species Using the Candidate Gene Approach

Bamboos are one of the most beautiful and useful plants on Earth.The genetic background and population structure of bamboos are well known,which helps accelerate the process of artificial domestication of bamboo.Partial sequences of six genes involved in nitrogen use efficiency in 32 different bamboo species were analyzed for occurrence of single nucleotide polymorphisms(SNPs).The nucleotide diversityθw and total nucleotide polymorphismsπT of the sequenced DNA regions was 0.05137 and 0.03332,respectively.Bothπnonsyn/πsyn and Ka/Ks values were<1.The nucleotide sequences of these six genes were inferred to be relatively conserved,and the haplotype diversity was relatively high.The results of evolutionary neutrality tests showed that the six genes were in line with neutral evolution,and that the NRT2.1 and AMT2.1 gene sequences may have experienced negative selection.An inter-SNP recombination event at the NRT2.1 gene in the all pooled sample,of all 32 bamboo species was the lowest at 0.0645,whereas the AMT gene recombination events were all>0.1.Estimation and analysis of linkage disequilibrium of five genes revealed that with the increase in nucleotide sequence length,the degree of SNP linkage disequilibrium decreased rapidly.We inferred the population genetic structure of 32 bamboo species based on the SNP loci of six genes with frequencies>18%.32 bamboo species were divided into five categories,which indicated that the combined population of all bamboo species had obvious multivariate characteristics and was heterogeneous;red(Group 1)and green(Group 2)were the main groups.