Correlation between Toll-like Receptor Gene Polymorphisms and Idiopathic Nephrotic Syndrome in Chinese Children

Objective Idiopathic nephrotic syndrome(INS)is the most common glomerular disease in children.Toll-like receptors(TLRs)have been reported to be associated with response to steroid treatment in children with INS.Nevertheless,the correlation between TLR genes and the progression of INS has not yet been clarified.The present study aimed to investigate the association of single-nucleotide polymorphisms(SNPs)in TLR2,TLR4,and TLR9 with susceptibility to INS as well as the clinical phenotyping of steroid responsiveness in Chinese children with INS.Methods A total of 183 pediatric inpatients with INS were included and given standard steroid therapy.Based on their clinical response to steroids,the patients were classified into three groups:steroid-sensitive nephrotic syndrome(SSNS),steroid-dependent nephrotic syndrome(SDNS),and steroid-resistant nephrotic syndrome(SRNS).A total of 100 healthy children were employed as controls.The blood genome DNA was extracted from each participant.Six SNPs(rs11536889,rs1927914,rs7869402,rs11536891,rs352140,and rs3804099)in TLR2,TLR4,and TLR9 were selected and detected by multiplex polymerase chain reaction with next-generation sequencing to assess TLR gene polymorphisms.Results Among the 183 patients with INS,89(48.6%)had SSNS,73(39.9%)had SDNS,and 21(11.5%)had SRNS.No significant difference was found in the genotype distribution between healthy children and patients with INS.However,the genotype and allele frequencies of TLR4 rs7869402 were significantly different between SRNS and SSNS.Compared with patients with the C allele and CC genotype,patients with the T allele and CT genotype had an increased risk of SRNS.Conclusion TLR4 rs7869402 affected the steroid response in Chinese children with INS.It might be a predictor for the early detection of SRNS in this population.

Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury

Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly（D,L-lactide-co-glycolic acid） has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly（D,L-lactide-co-glycolic acid） into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced ceils prus the poly（O,L-lactide-co-glycolic acid） scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly（D,L-lactide-co-glycolic acid） scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury.

Novel mutation in the ligand-binding domain of the androgen receptor gene （1790p） associated with complete androgen insensitivity syndrome

Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAIS） produces a female external phenotype, whereas cases with partial androgen insensitivity （PALS） have various ambiguities of the genitalia. Mild androgen insensitivity （MAIS） is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone （T） and dihydrotestosterone （DHT） synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.

Novel Association of Killer Cell Immunoglobulin-like Receptor Genes with EBV-infectious Diseases in Children

Killer cell immunoglobulin-like receptors （KIRs） which are mainly expressed on natural killer （NK） cells are implicated in many virus infections. However, it is unclear whether or not KIRs are associated with susceptibility to Epstein-Barr virus （EBV） infection related diseases. Therefore, the purpose of our study was to investigate possible correlation between polymorphisms of KIR genes and infectious mononucleosis （IM）/EBV-associated hemophagocytic Iymphohistiocytosis （EBV-HLH）. The polymorphisms of KIR genes were detected by polymerase chain reaction with sequence-specific primers （PCR-SSP）. The results would contribute to clarify the association of KIRs with EBV induced diseases, and provide new insights into the role of NK cells and innate immune response against viral infections and/or subsequent progression.

The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

Association of single nucleotide polymorphism of vitamin D receptor gene start codon and the suscepbility to prostate cancer in Han nationality in Hubei, China

Aim: To investigate the single nucleotide polymorphism of vitamin D receptor (VDR) gene start codon in the Han nationality in Hubei and its relationship to the susceptibility to prostate cancel (PCa). Methods: The VDR genotypes were determined by poly-merase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 80 patients with PCa and 96 normal male controls from the Han nationality in Hubei, using endonuclease Fok. Direct sequencing was done in part of the PCR products. Results: The frequency distribution of Fok I alleles in this cohort all followed the Hardy-Weinberg equilibrium. The distribution of genotypes and alleles had no significant difference between PCa patients and the controls (P>0.05). Conclusion: There was no significant relationship between Fok I polymorphism of VDR gene start codon and PCa in the Han nationality in Hubei.

Androgen receptor gene polymorphism and sex hormones in elderly men:the Tromsøstudy

The aim of this study was to examine whether CAG/GGN repeats are significant modulators of serum concentrations of total and free testosterone(T)as well as of luteinizing hormone(LH)in elderly men.Sixty-nine 60-to 80-year-old men with subnormal T levels(≤11.0 nmol L^(-1))and 104 men with normal T levels taking part in a nested case-control study were used for these analyses.Sex hormones were measured and free T was calculated.The CAG and GGN polymorphisms in the androgen receptor gene were determined by polymerase chain reaction and subsequent direct sequencing.There were no differences in the CAG and GGN repeat lengths between the groups.In cross-sectional analyses of the whole cohort,total and free T were positively associated with CAG length(all P<0.05)before,but not after,waist circumference or body mass index was added to the model.CAG repeat lengths were weakly,but not independently,associated with total and free T.These findings indicate that when clinically evaluating T and LH levels in elderly men,the CAG and GGN repeat lengths do not need to be taken into consideration.

Polymorphisms of Exon 17 of Insulin-Receptor Gene in Pathogenesis of Human Disorders With Insulin Resistance

Objective To investigate the relationship between polymorphisms of insulin-receptor (INSR) gene and insulin resistance in a population-based study in China. Methods Polymerase Chain Reaction (PCR) was used to the amplify Exon 17 of INSR gene and all amplified products were analyzed by direct sequencing. Results Six single-nucleotide polymorphisms (SNPs) were found at the following loci: T to TC at the locus of 10699 (Tyr984), G to GC at the locus of 10731 (Glu994), Deletion G at the locus of 10798 (Asp1017), C to T/TC at the locus of 10923 (His1058), C to CA at the locus of 10954 (Leu1069), and T to TA at the locus of 10961 (Phe1071), which might not change the amino acid sequence. The data were in agreement with the test of Hardy-Weinberg balance (P>0.05). Among the 345 cases, all clinical indices were higher in males than in females except for HDL cholesterol (P<0.05). The proportion of insulin resistance in males (64.4%) was higher than that in females (35.6%, OR=1.83). It implied that the relative risk of developing insulin resistance in males was 1.83 times as high as that in females. The biochemical indices in different loci on Exon 17 showed that the individuals with deletion G on the locus of 10798 had lower TG (P=0.052) and higher HDL (P=0.027) than those without deletion G on the same site. Homa-Index was lower in those with deletion G than in those without deletion G (P>0.05). After sex stratification in analysis, all allele frequencies on the six loci of SNPs of Exon 17 had different distributions between the insulin resistant group and the control group, but P>0.05. Conclusion SNPs of Exon 17 of INSR gene are unlikely to play a direct role in the pathogenesis of human disorders with insulin resistance.

Associations Between Epidermal Growth Factor Receptor Gene Mutation and Serum Tumor Markers in Advanced Lung Adenocarcinomas: A Retrospective Study

Objective To investigate the associations between epidermal growth factor receptor （EGFR） gene mutations and serum tumor markers in advanced lung adenocarcinomas. Methods We investigated the association between EGFR gene mutations and clinical features, including serum tumor marker levels, in 97 advanced lung adenocarcinomas patients who did not undergo the treatment of EGlaR tyrosine kinase inhibitors. EGFR gene mutation was detected by real-time PCR at exons 18, 19, 20, and 21. Serum tumor marker concentrations were analyzed by chemiluminescence assay kit at the same time. Results EGFR gene mutations were detected in 42 （43%） advanced lung adenocarcinoma patients. Gender （P=0.003）, smoking status （P=0.001）, and abnormal serum status of carcinoembryonic antigen （CEA, P=0.028） were significantly associated with EGFR gene mutation incidence. Multivariate analysis showed the abnormal CEA level in serum was independently associated with the incidence of EGFR gene mutation （P=0.046） with an odds ratio of 2.613 （95% Ch 1.018-6.710）. However, receiver operating characteristic （ROC） curve analysis revealed CEA was not an ideal predictive marker for EGFR gene mutation status in advanced lung adenocarcinoma （the area under the ROC curve was 0.608, P=0.069）. Conclusions EGFR gene mutation status is significantly associated with serum CEA status in advanced lung adenocarcinmoas. However, serum CEA is not an ideal predictor for EGFR mutation.

Fluoride Exposure,Follicle Stimulating Hormone Receptor Gene Polymorphism and Hypothalamus-pituitary-ovarian Axis Hormones in Chinese Women

The effects of fluoride exposure on thefunctions of reproductive and endocrine systemshave attracted widespread attention in academiccircle nowadays. However, it is unclear whether thegene-environment interaction may modify thesecretion and activity of hypothalamus-pituitary-ovarian （HPO） axis hormones. Thus, the aim of thisstudy was to explore the influence of fluorideexposure and follicle stimulating hormone receptor（FSHR） gene polymorphism on reproductivehormones in Chinese women. A cross sectionalstudy was conducted in seven villages of HenanProvince, China during 2010-2011. A total of 679women aged 18-48 years were recruited throughcluster sampling and divided into three groups, i.e.endemic fluorosis group （EFG）, defluoridationproject group （DFPG）, and control group （CG） basedon the local fluoride concentration in drinkingwater. The serum levels of gonadotropin releasinghormone （GnRH）, follicle stimulating hormone（FSH）, luteinizing hormone （LH）, and estradiol （E2）were determined respectively and the FSHRpolymorphism was detected by real time PCR assay.The results provided the preliminary evidenceindicating the gene-environment interaction onHPO axishormones in women.

Association between essential hypertension and polymorphisms of beta 1 adrenergic receptor gene G1165C (Gly389Arg) in Chinese Mongolian population

BACKGROUND： The prevalences of hypertension, cerebrovascular diseases, etc. are higher in Mongolian population because of the influence of various factors including genetics, geography, diet, etc. Therefore, it is helpful to develop researches on the genetics of various diseases including hypertension in Mongolian population. OBJECTIVE： To analyze the association between the polymorphism of beta1 adrenergic receptor （β1-AR） gene G1165C （Arg389Gly）, an important candidate gene for various diseases of cardiovascular system, and essential hypertension in Mongolian population. DESIGN ： A cross-sectional study SETTINGS： Department of Neurology, the First Affiliated Hospital of Inner Mongolia Medical College; Wulate Houqi Red Cross Society. PARTICIPANTS： The survey was carried out from February 2003 to March 2005. Totally 239 Mongolian residents, whose blood relations of 3 generations were all Mongolians, were selected from Wulate Houqi, Inner Mongolia, and they were all informed with the survey and detected items. Based on the diagnostic standard of hypertension set by WHO in 1999, the subjects were divided into two groups according to the level blood pressure： ① Normal blood pressure group （n=117）： systolic blood pressure （SBP） 〈 140 mm Hg （1 mm Hg =0.133 kPa）, diastolic blood pressure （DBP） 〈 90 mm Hg, and those having histories of cerebrovascular disease, heart disease, diseases of liver, kidney and tiroides, and diabetes mellitus were excluded. ② Essential hypertension group （n=122）： including 51 patients with simple high SBP. All the enrolled subjects had no blood relationship with each other, and had no history of miscegenation. METHODS ： The body height, body mass, waist circumference and blood lipids were measured routinely, and their habits of smoking and drinking were also investigated. Penpheral venous blood （5 mL） was drawn, the genome DNA was extracted, and the polymorphisms of the β1-AR Gl165C （Gly389Arg） genotype were detected with the Sequenom system. Polymerase chain reaction （PCR） experiment and SNP detection were performed in Huada Gene Laboratory of Bejing, then the univariate analysis of variance was applied in the sample comparison among groups, and the chi-square test was used to compare the genotypes and allele frequencies. The odd ratio （OR） and 95% confidence interval （CO were calculated. MAIN OUTCOME MEASURES： The distributions of β1-AR Gl165C （Gly389Arg） genotypes and alleles were observed. RESULTS： A11 the 239 subjects were involved in the analysis of results, and no one missed, ①Comparison of β1-AR G1165C （Gly389Arg） genotypes and allele distnbutions： In Mongolian population, the frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site in the essential hypertension group （72%, 28%） were not significantly different from those in the normal blood pressure group （67%, 33%） （xz=0.841, P=-0.359; OR 0.773, 95%Cl： 0.445-1.342）; The frequencies of C and G alleles also had no significant differences between the essential hypertension group （85%, 15%） and the normal blood pressure group （82%, 18%） （x^2=1.136, P=-0.287; OR： 0.769, 95%Cl： 0.747-1.248）. ②The frequencies of CC and GG＋GC genotypes at β1-AR G1165C （Gly389Arg） site had no significant differences between the patients with simple high SBP （71%, 29%） and the normal blood pressure group （x^2=0.250, P=-0.617; OR： 0.833, 95%C/： 0.408-1.703）; The frequencies of C and G alleles were not significantly different between the patients with simple high SBP （86%, 14%） and the normal blood pressure group （x^2=0.670, P=-0.413; OR 0.766, 95%Cl： 0.404-1.453）. CONCLUSION： In Mongolian population, the distributions of the genotypes and alleles of β1-AR Gl165C （Gly389Arg） have no obvious differences between the subjects with normal blood pressure and the patients with essential hypertension （including simple SBP increase）, which suggests that G1165C （Glu389Asp） site of β1-AR gene may be not a genetic mark of essential hypertension and simple high SBP in Mongolian population.

Study of Mutation in Tyrosine Protein Kinase of Insulin Receptor Gene in Patients with Polycystic Ovarian Syndrome

Objective To explore the molecular mechanism of insulin resistance in the patients with polycystic ovarian syndrome (PCOS)Methods Polymerase chain reaction, silver staining-single strand conformation poly-morphism(PCR-SSCP) and DNA direct sequencing were used to detect the mutation of insulin receptor (INSR) gene in exon 17-21 with the abdominal wall adipose tissue from 31 patients with PCOS (PCOS Group) and 30 patients with pure hysteromyoma in reproductive lift (Control Group).Results Tiventy-two variant SSCP patterns in exon 17 of INSR gene were detected. Direct sequence analysis of exon 17 showed that homozygous nonsense mutation was two alleles single nucleotide polymorphism (SNP) at the codon 1058 (CAC→CAT). Exons 18-21were not detected with any significantly mutation. The INSR gene His1058C→ T substitution collecting rate and insulin resistance were significantly higher in the PCOS group than in the control group (P = 0. 0293, P<0. 05, P<0. 01). Conclusion It is suggested that the SNP in codon 1058 of the INSR gene might be related with the insulin resistance in PCOS patients, which has hereditary tendency. And the missense mutation,nonsense mutation and frameshift mutation at exons 18-21 in tyrosine protein kinase region of INSR gene for PCOS patients were not frequently observed.

Complete androgen insensitivity syndrome caused by the c.2678C>T mutation in the androgen receptor gene:A case report

BACKGROUND Androgen insensitivity syndrome is an X-linked recessive genetic disease caused by mutations in the androgen receptor gene(AR).However,the underlying molecular mechanisms for the majority of AR variants remain unclear.In this study,we identified a point variant in three patients with complete androgen insensitivity syndrome(CAIS),summarized the correlation analysis,and performed a literature review.CASE SUMMARY The proband was raised as a girl.In infancy,she was first referred to hospital with a right inguinal hernia.Ultrasonography revealed the absence of a uterus and ovaries,and a testis-like structure located at the inguinal canal.Further diagnostic workup detected a 46,XY karyotype,and fluorescence in situ hybridization analysis showed the presence of the SRY gene.Histological analysis revealed the excised tissue to be testicular.Twelve years later,she was admitted to our hospital with a lack of breast development.Her pubic hair and breasts were Tanner stage I.She had normal female external genitalia.Blood hormone tests showed normal testosterone levels,low estradiol levels,and high gonadotropin levels.Her two siblings underwent similar examinations,and all three had a rare hemizygous missense mutation in AR:c.2678C>T.In vitro functional analyses revealed decreased nuclear translocation in AR-c.2678C>T mutation cells.CONCLUSION This case of CAIS was caused by an AR variant(c.2678C>T).Functional studies showed impaired nuclear translocation ability of the mutant protein.

The Relationship of Insulin-receptor Gene Polymorphism to Ischemic Stroke?

Objective\ To investigate the role of mutation of insulin receptor (INSR) gene in the development of ischemic stroke. Methods\ The base variations at exon 17 and 20 of INSR gene, by means of PCR SSCP were determined in 68 cases of atherothrombotic cerebral infarction (ACI), 81 cases of lacunar infarction (LI) and 62 healthy controls (HC). Results\ There were 2 alleles of T and C at exon 17 of INSR gene. The prevalence of mutant of T allele in ACI patients was more common than that in the controls. The blood pressure and the parameters of lipid metabolism in the patients with mutant were higher than those in the controls with wild type gene. However, the correlative analysis showed that the polymorphism of INSR gene was not related statistically to the blood pressure. No base variation at exon 20 was found in the study. Conclusion\ The mutation at exon 17 of INSR gene, by promoting the development of atherosclerosis, may participate in the occurrence of ischemic stroke.\;

Genetic variations of beta 2-adrenergic receptor gene are associated with essential hypertension in Xinjiang Kazakans

Objective The aims of the present study were to investigate the associations of 46 A〉G, 79 C〉G, 491 C〉T and 659 C〉G genetic variants of the human beta 2-adrenergic receptor （β2-AR）, ADRB2, gene with essential hypertension （EH） in Xinjiang Kazakans population.Methods A gender-matched case-control （271 hypertensive cases and 267 normotensive controls） study was used to investigate the associations of the four variations in the coding region of ADRB2 with EH. The genotypes of the variants were identified by the polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP） methods. Results 46 A〉G, 79 C〉G and 659 C〉G polymorphisms were common in the Kazakan population, but 491 C〉T was a mutation （frequency ofT allele was only 0.003） and only found in EH group. The fxequency distributions of genotypes and alleles for 659 C〉G between the EH and control groups was significantly different （P〈0.05）, while those for 46 A〉G and 79 C〉G polymorphisms were not statistically different. Logistic regression analysis suggested that the G allele of 659 C〉G polymorphism was a risk factor for hypertension （minor allele vs common homo; odds ratio, 13.240, 95% CI, 4.052-43.274; P〈0.05）. Covariance analysis showed that systolic and diastolic blood pressure levels in GG＋CG group of 659 C〉G were significantly higher than those in the CC group, but no significant difference of blood pressure were found between common homo and minor allele for 46 A〉G and 79C〉G polymorphisms. Haplotype analysis showed that two hyplotypes, HI： 46A-79C-491C-523C（48%）and H5：46A-79C-491C-659G, were associated with EH.Conelusion ADRB2 genetic variants may play independent roles in the molecular genetic mechanism of EH in Xinjiang Kazakans population （d Geriatr Cardio12010; 7：52-57）.

Study on PRRSV Receptor Genes Differential Expression in Lung Tissues in Different Breeds of Pigs after Infecting with HP-PRRSV

[ Objective] In order to study the susceptibility molecular mechanism of highly pathogenic porcine reproductive and respiratory syndrome virus （ HP- PRRSV） JXA1 isolate on Tibetan pig, Zangmei pig and Yorkshire pig. [ Method ] In the study, real-time quantitative RT-PCR method was established to compare and analyze the differential expression of five porcine reproductive and respiratory syndrome virus （PRRSV） receptor genes （HSPG2, SIGLEC1, CD163, VIM and NMMHC-H A） in lung tissues in Tibetan pig, Zangmei pig and Yorkshire pig before the challenge and at the 4th ,7th and 14th days after the challenge with JXAI isolate. [ Results ] HSPG2 expression in Tibetan pig lung tissues increased significantly at the 4th and 14th days after the challenge with JXAI （ P 〈 0.05 ）, while decreased significantly at the 7th day after the challenge （P 〈 0.05 ）, HSPG2 expression in Zangmei pig lung tissues increased significantly at the 14th day after the challenge （P〈0.05）. SIGLECl expression in Tibetan pig lung tissues increased significantly at the 4th and 14th days after the infection（P 〈 0.05 ）, while SIGLEC 1 expression in Yorkshire pig decreased significantly at the 4th, 7th and 14th days after the challenge （P 〈0. 05 ）. CD163 expression in lung tissues of Tibetan pig and Zangmei pig both increased significantly at the 14th day after the challenge （P 〈 0.05 ）, while CD163 expression in lung tissues of Yorkshire pig decreased significantly at the 7th and 14th days after the challenge （ P 〈 0. 05 ）. VIM expression in lung tissues of Tibetan pig increased significantly at the 7th day after the challenge （ P 〈 0. 05 ）, while which of Yorkshire pig at the 7th day after the challenge decreased significantly （ P 〈 0. 05 ）. NMMHC-II A expression in lung tissues of Zangmei pig increased significantly at the 4th day after the challenge （ P 〈 0. 05 ）, and which of Yorkshire pig increased significantly at the 4th and 14th days after the challenge （P 〈 0. 05 ）. [ Conclusion] SIGLEC1 and VIM genes might be the potential key genes affecting the susceptibility of JXA1 isolate on Tibetan pig, Zangrnei pig and Yorkshire pig. Key words JXA1 isolate; Tibetan pig; Zangmei pig; Yorkshire pig; Porcine reproductive and respiratory syndrome virus receptor genes; Differential expression

Genetic variants of the class A scavenger receptor gene are associated with coronary artery disease in Chinese

The class A scavenger receptor, encoded by the macrophage scavenger receptor 1 （MSR1） gene, is a pattern recognition receptor （PPR） primarily expressed in macrophages. It has been reported that genetic polymorphisms of MSR1 are significantly associated with the number of diseased vessels and coronary artery narrowing greater than 20% in Caucasians. However, whether it links genetically to coronary artery disease （CAD） in Chinese is not defined. Here, we performed an independent case-control study in a Chinese population consisting of 402 CAD cases and 400 controls by genotyping ten single nucleotide polymorphisms （SNPs） of MSR1. We found that rs416748 and rs13306541 were significantly associated with an increased risk of CAD with per allele odds ratio （OR） of 1.56 [95% confidence interval （CI） = 1.28-1.90; P 〈 0.001] and 1.70 （95% CI = 1.27-2.27; P 〈 0.001）, re- spectively. Our results indicate that genetic variants of MSR1 may serve as predictive markers for the risk of CAD / in combination with traditional risk factors of CAD in Chinese population.

Polymorphism of Follicle-Stimulating Hormone Receptor Gene in Ningxia Tan Sheep

[ Objective] To study the polymorphism of follicle-stimulating hormone receptor （FSHR） gene in Ningxia Tan sheep and thus to provide a theoretical basis for breeding. I Methodl Genotypes of 111 healthy Ningxia Tan sheep were examined by polymerase chain reaction and restriction fragment length polymorphism （PCR-RFLP）. [ResultS] A 306-bp fragment was amplified. The PCR products digested with restriction enzyme Alu I showed polymorphism with three genotypes, L e., GG, CG and CC. The genotypic frequencies of GG, CG and CC were 0.135 1 （ 15 individuals）, 0.666 7 （74 individuals） and 0.198 2 （22 individuals）, respectively. The allele frequencies of G and C were 0.468 5 and 0.531 5, respectively.[ Conclusion] FSHR aene is Dolvmomhic in Ninaxia Tan Sheeo.

Relationship between the low density lipoprotein receptor gene polymorphism and serum lipid levels in the Guangxi Bai Ku Yao population

Objectives Bai Ku Yao(White-trousers Yaos)is a special branch of Yao minority in China.They are now living in both Lihu and Baxu villages,Nandan County, Guangxi,China.The population size is about 30,000.The special customs and culture of Bai Ku Yao,including their special clothing,intra-ethnic marriages and alcohol intake are still completely conserved to the present day.In previous epidemiologic studies,we found that the serum lipid levels and the prevalence of hyperlipidaemia were lower in Bai Ku Yao than in Han Chinese from the same region.This ethnic difference in serum lipid profiles is still not well known.We hypothesized that there may be significant differences in some genetic polymorphismsssociation of low density lipoprotein receptor (LDL-R) genepolymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.Methods A total of 1024 subjects of Bai Ku Yao and 792 participants of Han Chinese were stud- ied by a stratified randomized cluster sampling.Epidemiological survey was carried out using internationally standardized methods.Information on demographics,socioeconomic status, and lifestyle factors was collected with standardized questionnaires. The height,weight,waist circumference,blood pressure, and serum total cholesterol(TC),triglyceride(TG), high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),apolipoprotein(Apo) A1, and ApoB were measured.Body massindex(BMI,kg/m2) was calculated.Genotyping of the LDL-RAvaⅡwas performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing.Results(l)The height,weight,serum TC,HDL-C,LDL-C,ApoAl levels and the ratio of ApoAl to ApoB were lower in Bai Ku Yao than in Han Chinese(P【0.01 for all),whereas the percentage of subjects who consumed alcohol or smoked cigarettes was higher in Bai Ku Yao than in Han Chinese(P【0.01 for each).(2) The frequency of A+ allele in Bai Ku Yao was 34.5%,and the frequencies of A-A-,A-A+ and A+A + genotypes were 42.6%,45.9%and 11.5%;respectively. The frequency of A+ allele in Han Chinese was 19.3%(P【0.001),and the frequencies of A-A-,A-A + and A+A+ genotypes were 64.9%,31.6%and 3.5%(P【0.001);respectively. The frequencies of A-A-,A-A+ and A+A+ genotypes in Bai Ku Yao were significant difference between males and females,between normal TC and high TC subgroup, and between normal LDL-C and high LDL-C subgroup (P【0.05 for all),whereas the frequencies of A- and A+ ? alleles in Han Chinese were significant difference between males and females(P【0.05).(3) Serum LDL-C levels in Bai Ku Yao were significant difference among the A-A-, A-A+ and A+A+ genotypes(P【0.05),the A+ carriers had higher serum LDL-C levels.Serum HDL-C levels in Han Chiese were significant difference among the A-A-,A-A + and A+A+ genotypes(P【0.01),the A+ carriers had higher serum HDL-C levels.(4) After adjusting other factors,the prevalence of LDL-C abnormality was still higher in Han Chiese than in Bai Ku Yao.The prevalence of TC abnormality in Han Chinese was almost twice high as in Bai Ku Yao. The age and diet were common risk factor for TC abnormality. No effect of AvaⅡgenotype or alcohol consumption on the TC abnormality was found,but the combination of geno-type and alcohol consumption can increase the prevalence of TC abnormality[Exp(B) =(1.154)].Age was negatively cor- related with TG level.Conclusions Serum TC and LDL-C levels were lower in Bai Ku Yao than in Han Chinese.There were significant differences in the AvaⅡallele and genotype frequencies between the he A+ carriers in Bai Ku Yao had higher serum LDL-C levels,whereas the A+ carriers in Han had higher serum HDL-C levels.Interactions between alcohol consumption or cigarette smoking and the LDL-R AvaⅡgenotype were also observed.The differences in the serum lipid profiles between the two ethnic groups might partly result from different genotypic frequency of LDL-R AvaⅡpolymorphism or differentgene-enviromental interactions.Bai Ku Yao and Han population,the frequency of A + allele was higher in Bai Ku Yao than in Han.T between the two ethnic groups.Therefore,the aim of the present study was to detect the

Familial Hypercholesterolemia in an Azorean Family:A Novel Mutation in the Low-Density Lipoprotein Receptor Gene

Familial hypercholesterolemia (FH) is one of the most prevalent autosomal dominant inherited disorders. Mutations have been found in at least 3 genes: the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9). We report on an Azorean family with FH due to a novel mutation in the LDLR gene across three generations. The index-case was first seen at our endocrinology consultation at 12 years old, because of delayed growth and development. Laboratorial investigations revealed a complete failure of the anterior hypophysis due to a congenital malformation of the sella turcica. A total cholesterol of 313 mg/dL (90 - 190 mg/dL) and low-density lipoprotein cholesterol (LDL-C) of 262 mg/dL (<115 mg/dL) was found in routine blood tests. There was a paternal history of hypercholesterolemia, corneal arcus and myocardial infarction at an early age. Screening for mutations in LDLR gene was carried out. &#73n the affected cases, an intronic heterozygous point mutation (c.818-3C > G) causing a premature termination of transcription (stop codon) was identified.