Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

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.

Single Nucleotide Polymorphisms (SNPs) Discovery and Linkage Disequilib-rium (LD) in Forest Trees

With completion of the Populus genome sequencing project and the availability of many expressed sequence tags (ESTs) databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural popula-tions. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilib-rium (LD) rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD map-ping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of com-plex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.

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

Nucleotide diversity(π) 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 c DNA and genomic sequences of the encoding Lk LAC8 gene were isolated from the LACCASE expressed sequence tags of the Japanese larch transcriptome database using the rapid amplification of c DNA ends-polymerase chain reaction(RACE-PCR).The c DNA 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 Cu^(2+) binding sites and 11 glycosylation sites,thus belonging to the LACCASE family.The deduced protein sequence shared an 89% identity with the Pta LAC from Pinus taeda.A real-time PCR analysis showed that the Lk LAC8 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 Lk LAC8 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 Lk LAC8 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.

Single Nucleotide Polymorphisms (SNPs) of URAT1 (rs7932775) and ABCG2 (rs3825016) on Chronic Kidney Disease Patients with Hyperuricemia

Background: More and more chronic kidney disease (CKD) patients are accompanied with hyperuricaemia. As is known, hyperuricaemia is an independent hazard of both cardiovascular diseases (CVD) and chronic kidney diseases. We aim at identifying Single Nucleotide Polymorphism (SNP) difference of hURAT1 (rs7932775) and ABCG2 (rs3825016) on CKD patient with hyperuricemia and/or gout. Methods: All forty-two CKD patients were divided into two groups: hyperuricemia, and control group. 24 hours urine sample and serum were prepared for testing biochemistry parameters. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method is used to analyze hURAT1 and ABCG2 single nucleotide polymorphisms in different groups. Results: 17 patients have CT SNP of hURAT1 (rs7932775) and 13 patients have CT SNP of ABCG2 (rs3825016) in hyperuricemia group, while only 5 persons and 6 persons have the same mutations in control group respectively. 7 patients have CT SNP of both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group, while only 2 persons have the same mutations in control group. CT mutation rates of hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 60.7% (17/28) and 50% (13/28) respectively, higher than that of control group (35.7% (5/14) and 42.8% (6/14)). What is more, Double SNP mutations in both hURAT1 (rs7932775) and ABCG2 (rs3825016) in hyperuricemia group were 25% (7/28), higher than that of control group (14.2%, 2/14). Conclusion: There are higher mutation rates of CT SNP in hURAT1 (rs7932775) and/or ABCG2 (rs3825016) in hyperuricemia group. We can conclude that hyperuricemia is a high risk factor in progress of CKD, which is necessary to take measures of decreasing serum uric acid to delay CKD progress.

Development of organelle single nucleotide polymorphism (SNP) markers and their application for the identification of cytoplasmic inheritance patterns in Pyropia yezoensis (Bangiales,Rhodophyta)

The genus Pyropia contains several important cultivated species.Genetic research in nori species has mainly focused on the cell nucleus,with few studies on organelles(chloroplast and mitochondria).Due to the high copy numbers of organelles in cells,which influence the development and traits of algae,it is necessary to study their genetic mechanism.In this study,the marine red alga Pyropia yezoensis,an important economic macroalga,was selected as the study object.To investigate organelle(chloroplast and mitochondria)inheritance in P.yezoensis,the wild type RZ(maternal strain)was crossed with the red mutant HT(paternal strain)and 30 color-sectors from 11 F1 gametophytic blades were examined.The complete chloroplast and mitochondrial genomes of the red mutant(HT)were assembled for the first time.One reliable and stable single nucleotide polymorphism(SNP)loci filtrated by bioinformatics analysis was used as a molecular marker for chloroplast and mitochondrial DNA,respectively,in subsequent experiments.PCR amplification and sequence analysis showed that the haplotypes of color-sectors detected were consistent with those of the maternal parent,confirming that both chloroplast and mitochondrial genomes were inherited maternally in P.yezoensis.The inheritance pattern of organelles in P.yezoensis can be used to guide the hybridization and breeding of nori.Additionally,the organelle SNP markers developed in this study can be applied in subsequent genetic research.

Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer

Matrix metalloproteinases(MMPs) are implicated in cancer development and progression and are associated with prognosis.Single-nucleotide polymorphisms(SNPs) of MMPs,most frequently located in the promoter region of the genes,have been shown to influence cancer susceptibility and/or progression.SNPs of MMP-1,-2,-3,-7,-8,-9,-12,-13 and-21 and of the tissue inhibitor of metalloproteinases(TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors.The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.

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 between low molecular polypeptide 7 single nucleotide polymorphism and response to therapy in hepatitis C virus infection

AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibro-sis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.

Correlation between single nucleotide polymorphism of rs3811047 in IL-1 F7 gene and rheumatoid arthritis susceptibility among Han population in central plains of China

Objective:To discuss the association between single nucleotide polymorphism(SNP) of rs3811047 in IL-1 F7 gene and rheumatoid arthritis(RA) susceptibility among the Han population in central plains of China.Methods:A total of 276 RA patients admitted to our hospital from December 2009 to December 2011 together with 276 healthy physical examinees in the same period were chosen as the subjects.The typing for rs3811047 SNP in IL-1 F7 gene was carried out by using ligase detection reaction and polymerase chain reaction technique.And the frequency of each allele and genotypes distribution was calculated so as to evaluate the association between genotype distribution and RA susceptibility.Results:The frequency of A allele of rs3811047 in IL-1 F7 gene in RA group and control group was 16.27%and 17.68%,respectively,and that of G allele in two groups was 83.73%and 82.32%,respectively.The difference between two groups wasn’t statistical significant(P 】0.05).The frequency of genotype AA,AG and GG in RA group was 2.19%,27.84%and 69.97%,respectively,while that in control group was 2.94%,29.78%and 67.28%, respectively.The difference of distribution of three genotypes was not statistically significant (P 】0.05).RA patients with A allele were better than those without A allele in joint swelling index, rest pain,HAQ scoring and blood sedimentation.There was significant difference between two groups in above indexes(P【0.05/P【0.01).Conclusions:No significant correlation between RA susceptibility among the Han population in central plains of China and rs3811047 SNP inIL-1 F7 gene is observed.However,A allele of rs3811047 has certain influence on the condition of RA patients.

抗白垩病相关SNP位点C2587245T在意大利蜜蜂雄蜂幼虫中的抗性鉴定

【目的】基于抗白垩病相关单核苷酸多态性(single nucleotide polymorphism,SNP)位点C2587245T在意大利蜜蜂Apis mellifera ligustica雄蜂幼虫中白垩病抗性检验,验证该位点遗传稳定性和抗病性,为分子标记辅助育种在育种生产中直接应用提供技术支持。【方法】通过白垩病虫尸,在实验室条件下制备白垩真菌孢子悬液,通过形态学和分子生物学方法鉴定蜜蜂球囊菌Ascosphaera apis。使用无伤害方法提取意大利蜜蜂蜂蜂王DNA筛选出SNP位点C2587245T为C/C和T/T基因型的蜂王,并培育C/C和T/T基因型处女王,用二氧化碳刺激其产出雄蜂卵,选择C和T基因型2日龄意大利蜜雄蜂幼虫进行实验室培养,3日龄龄雄蜂幼虫接种5×10^(4)个孢子/μL的蜜蜂球囊菌悬液10 d,观测接种蜜蜂球囊菌后的C基因型和T基因型雄蜂幼虫的生长情况和存活率。【结果】通过无伤害提取DNA的方法可以在不影响意大利蜜蜂雄蜂幼虫正常生活的条件下提取出高质量的DNA;用本研究的饲养方法可以保证意大利蜜蜂雄蜂幼虫在实验室条件的正常生长发育。C基因型和T基因型意大利蜜蜂雄蜂3日龄幼虫接种蜜蜂球囊菌后在发病时间和发病症状等方面都有明显差异,C基因型雄蜂幼虫在表现疾病典型症状的时间上比T基因型雄蜂幼虫晚大约2 d;在接种蜜蜂球囊菌后6 d时两种基因型雄蜂幼虫表现出的症状差异最为明显。【结论】雄蜂由于其纯合单倍体的生物学特性,更方便验证SNP位点C2587245T纯合的抗病作用。SNP位点C2587245T为C基因型雄蜂幼虫具有良好的抗白垩病能力,并且SNP位点C2587245T具有稳定的遗传性,这些研究结果可为在蜜蜂抗病育种领域提供一种可靠的分子辅助标记,为后续雄蜂转录组测序、寻找雄蜂和工蜂在免疫相关基因表达方面的差异,尝试找到SNP位点C2587245T对白垩病所特有的抗病机制提供基础。

Single nucleotide polymorphisms in intron 1 and intron 2 of Larimichthys crocea growth hormone gene are correlated with growth traits

The growth hormone gene (GH) affects animal growth and is a potential target for genetic studies of variation related to growth traits. In this study, we analyzed single nucleotide polymorphisms (SNPs) in GH intron regions and their associations with growth traits in large yellow croaker, Larimichthys crocea, from Zhejiang and Fujian stocks. The results of PCR-single strand conformation polymorphism showed two haplotypes of intron 1, named AA and AB genotypes, in Zhejiang stock. AB exhibited an SNP at position 196 (G A) that was negatively correlated with body height and positively correlated with standard length/body height (P 0.05). Two different genotypes, CC and CD, were identified in intron 2 in Fujian stock, with CD showing an SNP at position 692 (T C). The CD genotype had a significantly positive correlation with both weight and total length (P 0.01). These basic data highlight the potential for using GH as a genetic marker of fish growth in marker assisted selection.

Single nucleotide polymorphism C677T in the methylenetetrahydrofolate reductase gene might be a genetic risk factor for infertility for Chinese men with azoospermia or severe oligozoospermia

瞄准：分析单个核苷酸多型性(SNP ) 的分发在 methylenetetrahydrofolate reductase (MTHFR ) 的 C677T 在有自发的精子缺乏或严重 oligozoospermia 和是的 252 个肥沃的中国人的 355 个不肥沃的中国病人的基因控制探索 SNP 和男不孕的可能的协会。方法：用聚合酶链反应(PCR ) ，限制碎片长度多型性技术，等位基因和在 MTHFR 基因的 SNP C677T 的遗传型分发在病人和 controls.Results 被调查：等位基因 T 的频率(40.9% 对 30.4% ， P = 0.002，机会定量[或]= 1.58， 95%confidence 间隔[CI ] ：1.24-2.02 ) 并且变异的同质接合体(TT )(18.3% 对 11.5% ， P = 0.023，或 =1.72， 95% CI：1.07-2.76 ) 象有等位基因(TT + CT ) 的搬运人一样(63.4% 对 49.2% ， P = 0.0005，或 =1.79， 95% CI：1.29-2.48 ) 在不肥沃的病人比在控制的那些显著地高。在耐心的层化以后，在在每耐心的亚群和控制组之间的 SNP 的分发的重要差别尚待。结论：我们的调查结果显示有在有男不孕的 MTHFR 基因的 SNP C677T 的一个协会，建议这多型性可能是为在中国人的男不孕的一个基因风险因素。

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.

基于转录组测序芒果抗细菌性角斑病SNP/In Del分析

旨在挖掘与芒果抗细菌性角斑病紧密联系的SNP/InDel位点,以进一步揭示芒果抗细菌性角斑病的遗传多样性和分子机理。试验材料为细菌性角斑病高抗品种‘热农1号’和高感品种‘凯特’,分别对两个品种接病菌后0d、2d、6d的果皮进行转录组分析,以基因组‘红象牙’作为参考,鉴定并分析芒果中SNP/InDel位点的特征。结果表明,‘凯特’和‘热农1号’分别获得32.77Gb和36.83Gb的数据量,每个样本过滤后的Q30均高于90%。将reads比对到芒果参考基因组上,两个品种共检测到1213112个SNP位点,62888个InDel位点,主要分布在内含子区、外显子区、基因间区和基因上下游区域。SNP中转换位点和颠换位点分别为751006个(61.91%)和462106个(38.09%),其中转换型中A->G略多,而A->T在颠换型中占多数;In Del位点插入和缺失分别每个样本平均有18769和25015个。生物信息学分析表明,全部的SNP和InDel位点所在的差异基因,主要参与分子功能有代谢途径、应答刺激和生物学调控等过程。

Expression analysis,single nucleotide polymorphisms within SIRT4 and SIRT7 genes and their association with body size and meat quality traits in Qinchuan cattle

Silent information regulator 2(Sir2) proteins, or sirtuins, are nicotine adenine dinucleotide(NAD)-dependent deacetylases that connect metabolism with longevity in lower organisms. In mammals, there are seven Sir2 homologs, namely, silent information regulators(SIRT1–7). SIRT4 and SIRT7 genes play a crucial role in regulating lipid metabolism, cellular growth and metabolism. This suggests that they are potential candidate genes for affecting body size and meat quality traits in animals. Hence, this study aimed to detect genetic variations of both SIRT4 and SIRT7 bovine genes in Qinchuan cattle, and to evaluate the effect of these variations on economically important body size and meat quality traits. Expression analysis using quantitative real-time PCR(q PCR) indicated that SIRT4 and SIRT7 were broadly expressed in all thirteen studied tissues. The expression of SIRT4 was higher in liver, muscle, and in subcutaneous fat tissue. In the case of SIRT7, the expression was higher in lung, abomasum, and subcutaneous fat. Using DNA sequencing, a total of three single nucleotide polymorphisms(SNPs) were identified within SIRT4 and SIRT7 genes in 468 Qinchuan cattle. These included one novel SNP within 3′ untranslated regions(UTR) of SIRT4(SNP1: g.13915A>G) and two novel synonymous substitutions in SIRT7(SNP2: g.3587C>T and SNP3: g.3793T>C). Statistical analyses indicated that all three SNPs could significantly influence some body size and meat quality traits in Qinchuan cattle. These novel findings will provide a background for application of bovine SIRT4 and SIRT7 genes in the selection program of Chinese cattle.

Single nucleotide polymorphism in DNA methyltransferase 3B promoter and its association with gastric cardiac adenocarcinoma in North China

AIM: To investigate the association between single nucleotide polymorphism (SNP)in promoter of the DNA methyltransferase 3B (DNNT3B) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarcinoma (GCA).METHODS: The hospital based case-control study included 212 GCA patients and 294 control subjects without overt cancer. The DNMT3B SNP was genotyped by PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The C/C genotype was not detected in both GCA patients and controls. In control subjects, the frequency of T/T and C/T genotypes was 94.9% and 5.1% respectively,and that of T and C alleles was 97.4% and 2.6%, respectively.The genotype and allelotype distribution in the GCA patients was not significantly different from that in controls (P = 0.34 and 0.33, respectively). When stratified by smoking status and family history of upper gastrointestinal cancer, significant difference in the genotype distribution was not observed between GCA patients and controls. The distribution of DNMT3Bgenotypes in GCA patients with or without lymphatic metastasis did not show significant difference (P = 0.42). CONCLUSION: The distribution of DNMT3BSNP in North China is distinct from that in Caucasians. Although this SNP has been associated with susceptibility to lung, head, neck and breast cancer, it may not be used as a stratification marker to predict susceptibility and lymphatic metastasis of GCA, at least in the population of North China.

Prevalent false positives of azoospermia factor a （AZFa） microdeletions caused by single-nucleotide polymorphism rs72609647 in the sY84 screening of male infertility

复合聚合酶链反应(PCR ) 广泛地被用来检测 Y 染色体 microdeletions，它是男不孕的主要原因之一。两个都， Andrology (EAA ) 和欧洲分子的遗传优秀网络(EMQN ) 的欧洲学院为精子缺乏因素的察觉推荐了 sY84 和 sY86 标记的使用一(AZFa ) microdeletion 在为男不孕测试的 DNA 期间。在这研究，总共 630 中国男性的 AZF microdeletion 的大规模分析包括健康精液施主(n=200 ) ，有正常精子计数(n=226 ) 和有 nonobstructive 精子缺乏或严重 oligozoospermia (n=204 ) 的病人的不肥沃的男性，被执行。从 Y 染色体的 AZF 区域的一系列九个标注顺序的地点(圣) 标记被用来检测 microdeletions。所有教材基于生物工学信息的国家中心的建议被设计。不平常地高的发生(73/630， 11.6 &#x00025；)sY84 不在但是 sY86 礼品遗传型在屏蔽的 AZFa microdeletion 被观察。定序胁腹 sY84 区域揭示了 73 个病人的一个总数与 sY84 不在但是 sY86 礼品遗传型从 5 &#x02032 在第五个底有 T-to-G transversion；反向的 sY84 教材的结束。这些流行假 positives，它是不仅在不肥沃的人观察了，而且在施主观察了，源于说出的单个核苷酸的多型性(SNP ) 在反向的 sY84 教材的指向的顺序的 rs72609647。我们的学习建议那一多型性能阻止的 rs72609647 的存在预先屏蔽在不肥沃的中国男性的 AZFa microdeletions 察觉的经常的假积极结果。给 SNP rs72609647 最近在一个中国个人，的深定序被发现当前的 EAA 和 EMQN 标准可以需要在不同人口之中被细看在教材绑定序列避免潜在的基因变化。

Identification of a Regulatory Single Nucleotide Polymorphism in the Adiponectin (APM1) Gene Associated with Type 2 Diabetes in Han Nationality

Objective To identify the genetic defects of the the adiponectin (APM1) gene that contribute to the development of type 2 diabetes (T2DM) and determine the functional single nucleotide polymorphisms (SNPs) in the APM1 gene associated with T2DM in Han nationality. Methods The APM1 gene 5’-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance (IGT) and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APM1 levels or metabolic parameters was statistically assessed. Results Three SNPs were identified in the APM1 gene 5’-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls (G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03). Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-L1 cell line. Conclusion SNP -11377 G/C in the proximal promoter region of the APM1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.

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.