Recently, the -160 C/A polymorphism, located within the regulatory region of E-cadherin promoter, has been shown to influence E-cadherin transcription by altering transcription factor binding. We examined the effect of this polymorphism on risk of gastric cancer and on histological classification of intestinal- and diffuse-type gastric cancer in 146 normal healthy individuals and 292 Korean gastric cancer patients. Genomic DNA samples were examined by polymerase chain reaction (PCR)-single strand conformational polymorphism (SSCP)-sequencing and confirmed by restriction fragment length polymorphism (RFLP). Unexpectedly, there was no significant difference in the genotype frequencies of the polymorphism between normal control and gastric cancer patients (x(2) test, p=0.433). The estimated odd ratio of C/C to A/A genotype in gastric cancer cases was 1.07 (95% confidence interval, 0.396-2.870). We also found no evidence for differences in risk for the intestinal- and diffuse-type gastric cancer. These results suggest that the -160 C/A polymorphism of the E-cadherin has no direct effect on the risk of Korean gastric cancer development and on its histological classification.
Alleles ; Cadherins/*genetics ; DNA/metabolism ; Genetic Predisposition to Disease ; Genotype ; Homozygote ; Human ; Korea ; Odds Ratio ; Polymerase Chain Reaction ; Polymorphism (Genetics) ; Polymorphism, Restriction Fragment Length ; *Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational ; *Promoter Regions (Genetics) ; Risk ; Stomach Neoplasms/*genetics ; Transcription, Genetic

Asian populations contain a variety of ethnic groups that have ethnically specific genetic differences. Ethnic variants may be highly relevant in disease and human differentiation studies. Here, we identified ethnically specific variants and then investigated their distribution across Asian ethnic groups. We obtained 58,960 Pan-Asian single nucleotide polymorphisms of 1,953 individuals from 72 ethnic groups of 11 Asian countries. We selected 9,306 ethnic variant single nucleotide polymorphisms (ESNPs) and 5,167 ethnic variant copy number polymorphisms (ECNPs) using the nearest shrunken centroid method. We analyzed ESNPs and ECNPs in 3 hierarchical levels: superpopulation, subpopulation, and ethnic population. We also identified ESNP- and ECNP-related genes and their features. This study represents the first attempt to identify Asian ESNP and ECNP markers, which can be used to identify genetic differences and predict disease susceptibility and drug effectiveness in Asian ethnic populations.
Asian Continental Ancestry Group ; Classification ; Disease Susceptibility ; DNA Copy Number Variations ; Ethnic Groups ; Genetic Variation* ; Genotype ; Humans ; Polymorphism, Single Nucleotide

Autoimmune diseases (AID) are a group of complex disorders due to antibodies acting on self-antigens causing damage to the body. AID has long been considered as the outcome of genetic and environmental interactions. In recent years, studies have shown that increased susceptibility to AID may be associated with single nucleotide polymorphisms and copy number variations of Toll like receptor 7 (TLR7) gene, which provided a clue to further understanding of the pathogenesis of AID. This paper provides a review of the recent advances in understanding of the roles of TLR7 gene single nucleotide polymorphisms and copy number variations in AID.
Animals ; Autoimmune Diseases ; genetics ; DNA Copy Number Variations ; Genetic Predisposition to Disease ; Humans ; Polymorphism, Single Nucleotide ; Toll-Like Receptor 7 ; genetics

OBJECTIVE: To explore the prevalence and characteristics of chromosomal abnormalities in abortuses during early pregnancy with single nucleotide polymorphism microarray (SNP-array). METHODS: For 520 abortuses, copy number variations (CNVs) in chorionic villi were analyzed with SNP-array. RESULTS: In 510 (98.1%) of the samples, the analysis was successful. Among these, 57.6% (294/510) of the samples were found to harbor clinically significant chromosomal abnormalities. 38.8% of the samples (198/510) had a normal result. 2.4% (12/510) of the samples harbored benign CNVs, and 1.2% (6/510) harbored variants of uncertain significance (VOUS). Aneuploidies, polyploidies, pathogenic CNVs and uniparental disomies (UPD) had accounted for 75.2% (221/294), 13.9% (41/294), 8.2% (24/294), and 2.7% (8/294) of the samples, respectively. 45,XO was the most common finding, which was followed by trisomy 16 and trisomy 22. 69,XXY was the most common polyploidy. CONCLUSION Chromosomal abnormalities are the main cause for early miscarriage, among which aneuploidies are most common. The prevalence of aneuploidies is significantly increased among women over 35. SNP-array analysis has the advantage of high success rate, high resolution and great accuracy, but the clinical significance of microdeletions/microduplications found by SNP-array can be difficult for interpretation.
Chorionic Villi ; Chromosome Aberrations ; Chromosome Disorders ; DNA Copy Number Variations ; Female ; Genetic Testing ; Humans ; Karyotyping ; Polymorphism, Single Nucleotide ; Pregnancy

OBJECTIVETo investigate the sequence polymorphism of mtDNA HV1,HV2 overlapping fragments and coding region encompassing position 8430-8673 in Hebei Han population.

METHODSPolymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) combined with sequencing method was used to detect the haplotype distribution of mtDNA in 100 Hebei Han individuals.

RESULTSNinety-one haplotypes were noted in 100 unrelated individuals. The gene diversity is 0.9985 and the random match probability is 0.0115. Compared with the Anderson sequence, 65 sites of different nucleotide sequences were noted, of which 44 sites were previously registered in MITOMAP, 12 sites were not registered and the gene mutations were different from MITOMAP at 9 positions.

CONCLUSIONThe obtained data suggest that these loci are valuable genetic markers for personal identification and thus could be used as basic data for the forensic application of mtDNA in Hebei province.

China ; DNA, Mitochondrial ; genetics ; Humans ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Polymorphism, Single-Stranded Conformational

OBJECTIVE: A recent study suggested that a single nucleotide polymorphism (SNP) at position nt 9250 (C to T) in exon 7 of the osteopontin (OPN) gene is strongly associated with the susceptibility to systemic lupus erythematosus (SLE). This study examined the possible association between a single nucleotide polymorphism (SNP) at position nt 9250 (C to T) and SLE and measured the serum levels of OPN in Korean patients with SLE. METHODS: A total of 39 patients with SLE and 104 healthy controls were enrolled in this study. SNP located at position 9250 in the OPN gene were genotyped using the restriction fragment length polymorphism (RFLP). The serum levels of OPN in 39 patients with SLE and 20 healthy controls were determined by enzyme-linked immunosorbent assay. RESULTS: The allele frequencies of C and T at this position in patients with SLE were 34.6 and 65.4, whereas those in the controls were 20.7 and 79.3 (p<0.05). The serum levels of OPN in 39 patients with SLE were significantly higher than that in 20 healthy controls (49.13+/-26.71 versus 28.49+/-18.39 ng/ml, p<0.05). The increase in OPN concentration was associated with the SLE disease activity index (SLEDAI) score in all SLE patients (r=0.337, p<0.05). CONCLUSION: The allele frequencies of Eta-1/osteopontin were significantly associated with SLE. Moreover, the increased serum level of OPN is associated with the SLE disease activity. However, further investigation in larger groups in Korea will be needed.
Enzyme-Linked Immunosorbent Assay ; Exons ; Gene Frequency ; Humans ; Korea ; Lupus Erythematosus, Systemic ; Osteopontin ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide

OBJECTIVETo explore the correlation between four tagSNPs of Eppin gene (rs6124715, rs2231829, rs2227290 and rs11594) and the risk of idiopathic male infertility in the Chinese Han population.

METHODSA total of 473 confirmed infertile patients (from March 2005 to March 2007) and 198 fertile male controls (March 2005 to February 2009) were selected from two hospitals in Nanjing. All the subjects were Han Chinese and came from Nanjing or its surrounding areas. 5 ml peripheral blood was drawn from each subject with informed consent. Four tagSNPs (rs6124715, rs2231829, rs2227290 and rs11594) in Eppin gene were analyzed by the PCR-restriction fragment length polymorphisms (PCR-RFLP) method. The serum testosterone level was evaluated by radioimmunoassay (RIA).

RESULTSThe genotype frequencies of AA,AC and CC at rs11594 were 76.3% (361/473), 20.1% (95/473) and 3.6% (17/473) respectively in the case group, while the frequencies in the control group were 75.3% (149/198), 24.2% (48/198), 0.5% (1/198) respectively, the differences were statistically significant (χ² = 7.73, P = 0.021), the CC genotype carriers had an increased risk of male infertility (OR = 7.02, 95% CI:0.93-53.19). In the combined genotype analysis, the haplotype CTGA carriers has significantly lower onset risk (OR = 0.18, 95% CI:0.06-0.53). In the two groups, the frequencies and the risk of male infertility were no statistically significant in rs6124715, rs2231829 and rs2227290 genotype.

CONCLUSIONSThe Eppin gene polymorphisms were correlated to the susceptibility to idiopathic male infertility. Among them, CC genotype at rs11594 could increase the risk of idiopathic male infertility.

Genotype ; Haplotypes ; Heterozygote ; Humans ; Infertility, Male ; Male ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Proteinase Inhibitory Proteins, Secretory

OBJECTIVE: There is asingle nucleotide polymorphism (SNP) in the exon 2 of the vitamin D receptor (VDR) gene that can be distinguished using the restriction endonuclease FokI, and accordingly divided into three genotypes: FF, Ff and ff. VDR-FokI polymorphism was the only known SNP that could alter the protein structure of VDR. CYP24A1 is the gene encoding vitamin D 24 hydroxylase and is a vitamin D responsive gene. The influence of rs2228570 on transcriptional activation by VDR in human gingival fibroblasts (hGF) and periodontal ligament cells (hPDLC) was investigated in this study. METHODS: hGF and hPDLC of 12 donors' were primarily cultured and genomic DNA was extracted. A part of genomic DNA with the length of 267 bp was obtained using PCR, which contained the SNP. VDR-Fok I genotypes were determined according to the results of restriction fragment length polymorphism. hGF and hPDLC were stimulated with 10 nmol/L 1α,25 dihydroxy vitamin D₃ (1,25OH₂D₃) or 1 000 nmol/L 25 hydroxy vitamin D₃ (25OHD₃) for 48 h before RNA was extracted. Then VDR antagonist ZK159222 was used or not used during 1,25OH₂D₃ or 25OHD₃ stimulation with hGF and hPDLC. After 1,25OH₂D₃ stimulation for 48 h, the proteins in hGF and hPDLC were also collected. The protein expressions of CYP24A1 and VDR were detected using Western blot. RESULTS: Among the 12 donors' cell cultures, the number of FF, ff and Ff genotypes was 4, 3 and 5, respectively.After stimulation with 1,25OH₂D₃ or 25OHD₃ for 48 h,CYP24A1 mRNA levels in FF-hGF were significantly higher than those in other hGF genotypes(1,25OH₂D₃: F=31.147, P<0.01; 25OHD₃: F= 32.061,P <0.01), as was in FF-hPDLC (1,25OH₂D₃: F=23.347, P<0.01; 25OHD₃: F=32.569,P<0.01). When ZK159222 was used before 1,25OH₂D₃ stimulation, this statistically significant difference disappeared (hGF: F=0.246, P=0.787; hPDLC: F=0.574, P=0.583). When ZK159222 was used before 25OHD₃ stimulation, the trend was similar (hGF: F=1.636, P=0.248; hPDLC: F=0.582, P=0.578).After stimulation with 1,25OH₂D₃ for 48 h, CYP24A1 protein levels in FF-hGF were significantly higher than those in the other hGF genotypes (F=12.368, P <0.01), as was in FF-hPDLC (F=15.749, P <0.01). In hGF and hPDLC, the mRNA or protein expression of VDR of different genotypes was not significantly different under different stimulation conditions.The paired comparison showed that there was no statistically significant difference between the expression of CYP24A1 in hGF and that in hPDLC under all the stimulation conditions, as was the expression of VDR. CONCLUSION In hGF and hPDLC, the FF-VDR genotype is associated with the more remarkable up-regulation of CYP24A1than the other genotypes, indicating that transcriptional activation of FF-VDR might be higher than those of other vitamin D receptors.
Fibroblasts/metabolism* ; Genotype ; Humans ; Periodontal Ligament/metabolism* ; Polymorphism, Genetic ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Receptors, Calcitriol/genetics* ; Vitamin D3 24-Hydroxylase/metabolism*

The development of Human Genome Project (HGP) makes it possible and more important to reveal the variations or polymorphisms precisely between different individuals and populations. Due to the characters of their high polymorphism and value in disease-linkage analysis as well as pharmacogenomnics, genetic markers on X chromosome have attracted much more attention of current medical and forensic scientists. This report summarized the proceeding of research on X chromosome genetic markers in the clinical and forensic context.
Chromosomes, Human, X/genetics* ; Female ; Genetic Markers ; Genetic Variation/genetics* ; Humans ; Microsatellite Repeats/genetics* ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide

OBJECTIVETo investigate the genetic association for schizophrenia within the long arm region 1 band 1 of chromosome 22 (22q11) in a Han Chinese population.

METHODSPolymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis was used to detect three single nucleotide polymorphism (SNPs), rs165655 (A/G base change) and rs165815 (C/T base change) present in the ARVCF (armadillo repeat gene deletion in velocardiofacial syndrome) locus, and rs756656 (A/C base change) in the LOC128979 (expressed sequence tags, EST) locus, among 100 nuclear families composed of fathers, mothers and affected offspring with schizophrenia. Genotyping data were analyzed by linkage disequilibrium methods including haplotype relative risk (HRR) analysis, transmission disequilibrium test (TDT) and haplotype transmission analysis.

RESULTSThe genotype frequency distributions of three SNPs were all in Hardy-Weinberg equilibrium; Both HRR and TDT analysis showed that rs165815 was associated with schizophrenia (P < 0.05), whereas the other two SNPs did not show any allelic association. The haplotype transmission analysis showed a biased transmission for the rs165655-rs165815 haplotype system and for the rs756656-rs165655-rs165815 haplotype system (P < 0.01).

CONCLUSIONEither ARVCF gene itself or a nearby locus might confer susceptibility to schizophrenia in a Han Chinese population.

Adult ; Chromosomes, Human, Pair 22 ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Haplotypes ; Humans ; Linkage Disequilibrium ; genetics ; Male ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Schizophrenia ; genetics