Genetic variation in the TP63 gene is associated with lung cancer risk in the Han population.

Lung cancer is one of the most common malignant tumors that seriously threaten human health. Current evidence suggests that heredity contributes to the progression of lung cancer. To investigate and validate potential genetic associations with the risk of lung cancer, we conducted a case-control study including 309 cases and 310 controls from Xi'an City, which is located in northwest China, and genotyped six SNPs in five genes, which are related to metabolic process. Overall, our results show that the SNP rs10937405 was associated with a decreased occurrence of lung cancer (OR = 0.72; 95% CI = 0.56-0.92; p = 0.009). In the genetic models analysis, we found that genotype "CT" of rs10937405 in TP63 was associated with a decreased lung cancer risk (OR = 0.71; 95% CI, 0.51-0.99; p = 0.031); the genotype "TT" of rs10937405 showed a decreased lung cancer risk in the co-dominant model (OR = 0.53; 95% CI, 0.30-0.95; p = 0.031). The genotype "CT-TT" of rs10937405 also showed a decreased lung cancer risk in the dominant model (OR = 0.67; 95% CI, 0.49-0.92; p = 0.014) and the log-additive model (OR = 0.72; 95% CI, 0.56-0.92; p = 0.0085). The genotype "CC-CT" of rs10937405 confers a higher risk of lung cancer for males than females. Our results, combined with those from previous studies, suggest that genetic variation in TP63 may influence lung cancer susceptibility in the Han population.

RTEL1 and TERT polymorphisms are associated with astrocytoma risk in the Chinese Han population.

Common variants of multiple genes play a role in glioma onset. However, research related to astrocytoma, the most common primary brain neoplasm, is rare. In this study, we chose 21 tagging SNPs (tSNPs), previously reported to be associated with glioma risk in a Chinese case-control study from Xi'an, China, and identified their contributions to astrocytoma susceptibility. We found an association with astrocytoma susceptibility for two tSNPs (rs6010620 and rs2853676) in two different genes: regulator of telomere elongation helicase 1 (RTEL1) and telomerase reverse transcriptase (TERT), respectively. We confirmed our results using recessive, dominant, and additive models. In the recessive model, we found two tSNPs (rs2297440 and rs6010620) associated with increased astrocytoma risk. In the dominant model, we found that rs2853676 was associated with increased astrocytoma risk. In the additive model, all three tSNPs (rs2297440, rs2853676, and rs6010620) were associated with increased astrocytoma risk. Our results demonstrate, for the first time, the potential roles of RTEL1 and TERT in astrocytoma development.

[Polymorphism of fifteen short tandem repeat loci in Tibetan of Changdu area].

OBJECTIVE: To investigate the genetic polymorphism of 15 autosomal short tandem repeat (STR) loci, i.e. D5S818, FGA, D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX and D18S51, in Tibetan population of Changdu area, and to analyze the genetic relationship between this population and other Asian populations. METHODS: The 15 loci were amplified simultaneously using a multiplex PCR typing system. Amplified STR fragments were analyzed with an ABI PRISM 3100 Avant DNA Analyzer. Arlequin software version 3.1 was used to obtain allele frequencies and polymorphism parameters. RESULTS: There were 135 STR alleles in the 15 STRs of Changdu Tibetan, with allele frequencies ranging from 0.0065 to 0.5455. The average heterozygosity was 0.7340, the discrimination power was higher than 0.8 except for TPOX and TH01. The accumulative discrimination power was more than 0.9999998, and the accumulative non-parental exclusion probability was 0.99999997. CONCLUSION: The 15 STR loci of Changdu Tibetan possess characteristics of high genetic diversity. They can be employed in minority genetics investigation, and individual and paternity test in forensic medicine.

[Genetic polymorphism of 15 short tandem repeats loci of Tibetan nationality and its affinity with other nationalities in Tibet].

OBJECTIVE: To determine the genetic diversity of short tandem repeats (STRs) loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, upsilonWA, TPOX, D18S51, D5S818, and FGA), and to evaluate the genetic structure of Tibetan nationality and its affinity with other Tibetans (Changdu Tibetan, Luoba ethnic group, Deng population) and other Asian populations. METHODS: Fifteen STRs loci were amplified simultaneously using a multiplex PCR typing system. Amplified STR fragments were analyzed with an ABI PRISM 3100 Avant DNA Analyzer. Arlequin software version 3.1 was used to obtain allele frequencies and polymorphism parameters. The genetic distance (D(A)), coefficient of gene differentiation (Gst) values, and heterozygosity (Ht) were estimated using DISPAN. A phylogenetic tree from the allele frequency data at 8 STRs loci and 15 STRs loci obtained from the literature reported previously by using the D(A) and Neighbor-Joining (N-J) method was constructed using MEGA Version 4.0. Multidimensional scaling (MDS) analysis was performed using the SPSS 14.0 software package. RESULTS: We got 132 alleles in the population studied, with the frequency of 0.0050-0.5990. Ht, the power of discrimination (DP) and the polymorphism information content (PIC) were consistent with the forensic application. Cluster analysis and phylogenic trees revealed that Tibetan nationality had estrangement genetic affinity with other Chinese nationalities and Asian population. CONCLUSION: The genetic information demonstrates that the 15 chosen gene makers are highly informative loci and are suitable for population genetic research and forensic application.

[Genetic polymorphism analysis of 8 short tandem repeat loci on the X chromosome in Luoba population of China].

OBJECTIVE: To investigate the alleles and genotype frequency of 8 short tandem repeat (STR) loci (DXS6804, DXS8378, DXS7132, DXS7133, DXS6789, DXS101, HPRTB and DXS7423) on the X chromosome in Luoba ethnic group of China. METHODS: The eight X chromosome STR (X-STR) loci were analyzed by polymerase chain reaction (PCR) followed by polyacylamide gel electrophoresis and silver stain. RESULTS: Among 96 unrelated Luoba individuals, the numbers of alleles in the 8 X-STR loci (DXS7133, DXS6789, DXS6804, DXS8378, DXS101, DXS7424, DXS7132 and HPRTB) were 5, 8, 7, 5, 8, 8, 8 and 5, respectively. The genotype frequencies in females were in accordance with Hardy-Weinberg equilibrium. CONCLUSION: The eight X-STR loci are appropriate for individual identification, paternity testing involving a female child and studies on related diseases.

[Genetic polymorphisms of 14 Y-chromosomal short tandem repeat loci and haplotypes in Tibetan].

OBJECTIVE: To reveal the allelic frequencies and haplotype frequencies of fourteen Y-chromosome short tandem repeat (STR) loci in a Tibetan population. METHODS: The Y-chromosomal STR loci were analyzed from 126 healthy unrelated autochthonous male individuals of Chinese Tibetan using a multiplex PCR system. Allele and haplotype frequencies for these loci were determined by the AmpFISTR Y filer PCR Amplification kit. RESULTS: One hundred and twenty-one alleles were detected from the 14 STR loci. The allele diversity values (DP) for each locus ranged from 0.4104 (DYS391) to 0.9489 (DYS385a, b), the DP value of these loci were higher than 0.5 except for that of DYS391. A total of 105 haplotypes were identified in the Y-STR loci, among which 103 were unique, while two occurred more than once. The overall haplotype diversity for the Y-STR loci was 0.9998, and the discrimination capacity was 0.9898. CONCLUSION: The 14 STR loci above belong to loci of high discriminating ability, the haplotypes are highly polymorphic.

A panel of 74 AISNPs: Improved ancestry inference within Eastern Asia.

Many ancestry informative SNP (AISNP) panels have been published. Ancestry resolution in them varies from three to eight continental clusters of populations depending on the panel used. However, none of these panels differentiates well among East Asian populations. To meet this need, we have developed a 74 AISNP panel after analyzing a much larger number of SNPs for Fst and allele frequency differences between two geographically close population groups within East Asia. The 74 AISNP panel can now distinguish at least 10 biogeographic groups of populations globally: Sub-Saharan Africa, North Africa, Europe, Southwest Asia, South Asia, North Asia, East Asia, Southeast Asia, Pacific and Americas. Compared with our previous 55-AISNP panel, Southeast Asia and North Asia are two newly assignable clusters. For individual ancestry assignment, the likelihood ratio and ancestry components were analyzed on a different set of 500 test individuals from 11 populations. All individuals from five of the test populations - Yoruba (YRI), European (CEU), Han Chinese in Henan (CHNH), Rondonian Surui (SUR) and Ticuna (TIC) - were assigned to their appropriate geographical regions unambiguously. For the other test populations, most of the individuals were assigned to their self-identified geographical regions with a certain degree of overlap with adjacent populations. These alternative ancestry components for each individual thus help give a clearer picture of the possible group origins of the individual. We have demonstrated that the new AISNP panel can achieve a deeper resolution of global ancestry.

[Determination of HLA-A, B, and DRB1 gene polymorphism in Monba ethnic group of Xizang Autonomous Region, China].

OBJECTIVE: To investigate the HLA-A, B, DRB1 allele polymorphism in Monba ethnic population of Xizang Autonomous Region. METHODS: HLA-A, B, DRB1, DNA types in 47 unrelated Monba ethnic healthy individuals from the Xizang Autonomous Region of China were analyzed by polymerase chain reaction-based reverse line-strip sequence specific oligonucleotide hybridization. Based on the HLA-DRB1 alleles frequencies of 11 other ethnic groups in China, a molecular phylogenetic tree was constructed by the Neighbor-Joining (NJ) method. RESULTS: Twenty-three alleles were detected for HLA-A, 39 for HLA-B, and 33 for HLA-DRB1. HLA-A*1101, A*2402, A*02011, A*0206, HLA-B*3802, B*4001, B*4002, B*51011, HLA-DRB1*12021, DRB1*0403, DRB1*0701, DRB1*1201 were the most common alleles. The most frequent alleles were HLA-A*1101(0.2128), HLA-B*3802(0.1064), and HLA-DRB1*12021(0.0851). CONCLUSION: The HLA loci are highly polymorphic in Monba population of Xizang Autonomous Region. Compared with other ethnic groups in China, the Monba ethnic group is close to Tibetan ethnic group.

[Analysis of genetic polymorphism of 7 STR loci on chromosome 12 in Shaanxi Han populations].

To analyze the genetic polymorphism of 7 STR loci (D12S1718,D12S1675, D12S358, D12S367, D12S1638, D12S1646 and D12S1682) on chromosome 12 in Shaanxi Hans. EDTA-blood specimens were collected from 80 unrelated individuals from Chinese Han population in Shaanxi province. The DNA samples were extracted and relevant fragments were amplified by polymerase chain reaction (PCR). The PCR products were analyzed by ABI 3100 Genetic Analyzer. The number of alleles and genotypes observed at loci D12S1718, D12S1675, D12S358, D12S367, D12S1638, D12S1646 and D12S1682 were 7, 10, 8, 8, 6, 9, 11 for alleles and 10, 17, 18, 18, 14, 18, and 26 for genotypes, respectively. The heterozygosities for the 7 STR loci were 44.28%, 66.10%, 78.89%, 77.89%, 73.69%, 74.55% and 82.39%, respectively. The distribution of allele frequencies of 7 STR loci on chromosome 12 was consistent with Hardy-Weinberg equilibrium and relatively high genetic polymorphism was observed in Shaanxi Han population.

[Determination of HLA-DRB1 gene polymorphism in Luoba ethnic group of Tibet].

OBJECTIVE: To investigate the frequencies of allele and genotype of HLA-DRB1 gene in Luoba ethnic group. METHODS: HLA-DRB1 genes from 92 individuals of Luoba ethnic group in Tibet Autonomous region were investigated, using PCR-SSO (polymerase chain reaction -sequence specific oligo-nucleotide) genotyping methods. We compared allele frequencies of Luoba population in HLA-DRB1 locus with that of various ethnic groups distributed worldwide, constructed the phylogenetic tree by UPGMA (unweighted pair group method with arithmetic mean), and counted genetic distance by Nei measure. RESULTS: Of the 11 DRB1 alleles detected, the two most common genes were DRBI * 04( gene frequency: 27.20% ) and DRB * 12 (25.50%) , which covered 52.70% of the total alleles detected from Luoba ethnic group. The frequencies of HLA-DRB1 * 14(15.20% ), DRB1 * 15(9.80% ) and DRB1 * 08(8.20% ) were more than 5%. Luoba was unique in the distribution of HLA alleles. The genetic distance between Luoba and Tibetan was closer than that with other population. A dendrogram based on the DRB1 genes by cluster analysis suggested that Luoba ethnic group might cluster with Tibetan firstly, then cluster with other population living in China (except Uygr) , and cluster with Caucasian and Black finally. CONCLUSION: The HLA-DRBI gene frequency of Luoba individuals in Tibet Linzhi had some differences compared with that of other Chinese population. The kindred relation between Luoba and Tibetan was closer than that with other population, which was coincident with the results of ethnology, history and sociology.

Meta-analysis of the association between the rs8034191 polymorphism in AGPHD1 and lung cancer risk.

BACKGROUND: Possible associations between the single nucleotide polymorphism (SNP) rs8034191 in the aminoglycosidephosphotransferase domain containing 1 (AGPHD1) gene and lung cancer risk have been studied by many researchers but the results have been contradictory. MATERIALS AND METHODS: A computerized search for publications on rs8034191 and lung cancer risk was performed. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between rs8034191 and lung cancer risk with 13 selected case-control studies. Sensitivity analysis, test of heterogeneity, cumulative meta-analysis, and assessment of bias were also performed. RESULTS: A significant association between rs8034191 and lung cancer susceptibility was found using the dominant genetic model (OR=1.344, 95% CI: 1.285-1.406), the additive genetic model (OR=1.613, 95% CI: 1.503-1.730), and the recessive genetic model (OR=1.408, 95% CI: 1.319-1.503). Moreover, an increased lung cancer risk was found with all genetic models after stratification of ethnicity. CONCLUSIONS: The association between rs8034191 and lung cancer risk was significant using multiple genetic models, suggesting that rs8034191 is a risk factor for lung cancer. Further functional studies of this polymorphism and lung cancer risk are warranted.

Multiple genetic variants are associated with colorectal cancer risk in the Han Chinese population.

Colorectal cancer (CRC) is a major health burden worldwide and is the second-leading cause of cancer-related death in Europe. CRC is a complex disease resulting from a series of genetic and epigenetic changes that lead to a stepwise progression from normal mucosa to dysplasia and finally to carcinoma. In this study, we present genetic association results between 25 tag single-nucleotide polymorphisms and CRC in a case-control study (203 cases, 296 controls) of a Han Chinese population. We found that rs1143634 in the interleukin-1ß (IL1B) gene and rs1800871 in the interleukin-10 (IL10) gene were associated with increased risk for CRC in the Han Chinese. Further haplotype analysis revealed that the 'GAC' in the SMAD7 (mothers against decapentaplegic homolog 7) gene was found to increase CRC risk (odds ratio=1.48; 95% confidence interval, 1.09-2.01; P=0.012). Our results, combined with previous studies, suggest that IL10, PSCA, IL1B, and SMAD7 are significantly correlated with CRC susceptibility in the Han Chinese population.

Meta-analysis of the rs4779584 polymorphism and colorectal cancer risk.

PURPOSE: Several researchers have suggested that the rs4779584 (15q13.3) polymorphism is associated with an increased risk of developing colorectal cancer (CRC). However, past results remain inconclusive. We addressed this controversy by performing a meta-analysis of the relationship between rs4779584 of GREM1-SCG5 and colorectal cancer. METHODS: We selected 12 case-control studies involving 11,769 cases of CRC and 14,328 healthy controls. The association between the rs4779584 polymorphism and CRC was examined by the overall odds ratio (OR) with a 95% confidence interval (CI). We used different genetic model analyses, sensitivity analyses, and assessments of bias in our meta-analysis. RESULTS: GREM1-SCG5 rs4779584 polymorphisms were associated with CRC in all of the genetic models that were examined in this meta-analysis of 12 case-control studies. CONCLUSION: GREM1-SCG5 rs4779584 polymorphisms may increase the risk of developing colorectal cancer.

Association of polymorphisms in FLT3, EGFR, ALOX5, and NEIL3 with glioblastoma in the Han Chinese population.

Glioblastoma (GBM) is the highest-grade glioma in astrocytoma. Patients often have poor prognosis due to therapeutic resistance and tumor recurrence. Identification of the genetic factors of GBM could be important contribution to early prevention of this disease. We genotyped 17 tag single-nucleotide polymorphisms (tSNPs) from nine genes in this study, including 72 cases and 302 controls. SNP genotyping was conducted using Sequenom MassARRAY RS1000. Statistical analysis of the association between tSNPs and GBM was performed using the χ (2) test and SNPStats software. The rs3829382 in FLT3 was associated with increased odds of developing GBM using the χ (2) test. When we analyzed tSNPs under different inheritance models, we found rs9642393 in EGFR increased odds of developing GBM in the dominant model. After stratification by gender, we found that rs12645561 in NEIL3 and rs2291427 in ALOX5 were associated with developing GBM. Polymorphisms within FLT3, EGFR, NEIL3, and ALOX5 may contribute to the occurrence of GBM in the Han Chinese population. However, the functional significance of these polymorphisms needs further investigation.

Polymorphisms and phenotypic analysis of cytochrome P450 2D6 in the Tibetan population.

The cytochrome P450 2D6 enzyme (CYP2D6) metabolizes about 25% of prescribed drugs in the endoplasmic reticulum, and genetic polymorphisms in CYP2D6 can greatly affect its activity and lead to differences among individuals in drug efficacy and adverse drug reactions. To investigate genetic polymorphisms in CYP2D6 among Tibetan Chinese, we directly sequenced the whole gene in 96 unrelated, healthy Tibetans from The Tibet Autonomous Region of China and screened for genetic variants in the promoter, exons, introns, and 3'UTR. We detected fifty-one genetic polymorphisms in CYP2D6, and 16 of them are novel. The allele frequencies of CYP2D6*1, *2, *5, *10, *41, and *49 were 0.25, 0.43, 0.02, 0.29, 0.02, and 0.01, respectively. The frequency of CYP2D6*10, a putative poor-metabolizer allele, was lower in our sample population compared with that in the Han Chinese population (p<0.001). In addition, haplotype analysis allowed 15 CYP2D6 haplotypes to be classified into three groups. In conclusion, our results provide basic information about CPY2D6 alleles in Tibetans and suggest that the enzymatic activities of CYP2D6 may differ among the diverse ethnic populations of China. Our results provide a basis for safer drug administration and better therapeutic treatment among Tibetans.

[Transmission disequilibrium test for 15 short tandem repeat loci in Kashin-Beck disease and their interaction with low selenium].

OBJECTIVE: To identify the genetic susceptibility to Kashin-Beck disease (KBD) and explore the interaction between low selenium (Se) and the susceptibility gene loci in KBD. METHODS: The DNA samples collected from 23 KBD nuclear families were analyzed using PCR and GeneScan Analysis 3.7 and Genotyper3.7 software. The haplotype relative risk (HRR) and transmission disequilibrium test (TDT) were used to test the data of the genotypes. The serum selenium (Se) concentration was measured by atomic fluorescence spectrometry, and the interaction between low Se and the susceptibility loci was calculated using a binary logistic regression. RESULTS: In the 23 nuclear families, the alleles of D2S151 (248 bp), D2S305 (320 bp), and D11S4094 (194 bp) showed significant correlation to KBD (P<0.05). Serum Se concentrations in the studied individuals was 0.037 µg/ml. No significant statistical interaction was observed between low Se exposure and the susceptibility loci (P>0.05). CONCLUSION: The polymorphisms in the STR loci D2S305, D2S151, and D11S4094 or the polymorphism loci near them might been related to KBD susceptibility. Low Se exposure shows no significant interaction with the susceptibility loci.

Y chromosome STR haplotypes of Tibetan Living Tibet Lassa.

Allele frequencies and haplotypes of the 17 Y-chromosome STRs loci, namely DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 (YGATA C4), and YGATA H4 were determined in a sample of 131 healthy unrelated males from the Lassa area of Tibet Autonomy Region of China (SW China). In 131 samples 106 different haplotypes were encountered, of which 105 were observed only once. The overall haplotype diversity was 0.9998. The results demonstrate that these loci will be very useful for human identification in forensic cases and paternity tests in the Lassa region.

Allele frequencies of 15 STR loci of Tibetan lived in Tibet Lassa.

Allele frequency data for 15 Short Tandem Repeat (STR) loci included in the AmpFl STR Identifiler kit were obtained from a sample of 196 healthy unrelated individuals of Tibetan born in Lassa of Tibet Autonomy Region of China (SW China). The distribution of these observed genotypes were not significantly different from the expected distribution according to Hardy-Weinberg equilibrium.

[Changes of the content of Se and the levels of several cytokines in the serum of patients with Kaschin-Beck disease].

AIM: To investigate the levels of selenium (Se) and several cytokines (TNF-alpha, VEGF and IL-1beta) in the serum of patients with Kaschin-Beck disease (KBD). METHODS: 90 subjects were selected, from KBD areas and non-KBD areas of Lhasa, Tibet. Then they were divided into 3 groups: the group with KBD (30), the control in KBD areas (30), and the control in non-KBD areas (30). There was no obvious difference in sex and age in the three groups. The content of Se in the serum was detected by atomic fluorescent spectrometer and the level of cytokines (TNF-alpha, VEGF and IL-1beta) in the serum were detected by ELISA. RESULTS: The content of Se in the serum of persons living in the KBD-disease areas were lower than that of persons living in non-KBD disease areas. The levels of TNF-alpha, VEGF and IL-beta in KBD group were higher than those in normal control group (P<0.05). The content of Se had negative correlation with the levels of TNF-alpha and IL-beta in serum. CONCLUSION: The decrease of Se content and increase of the levels of TNF-alpha, VEGF and IL-1beta may play a role in pathogenesis of KBD.

[Serum hyaluronic acid, tumor necrosis factor -alpha, vascular endothelial growth factor, NO, and Se levels in adult patients with Kashin-Beck disease].

OBJECTIVE: To investigate the association of serum levels of hyaluronic acid (HA), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor (VEGF), NO, and Se with the clinical manifestations in adult patients with Kashin-Beck disease (KBD). METHODS: Total 216 adults were selected for KBD screening from the KBD-prevalent areas in Yongshou county and the non-KBD areas of Chang'an county, Xi'an city, ShaanXi Province. According to the National Diagnostic Criteria of Kashin-Beck Disease in China, the diagnoses of KBD was established in 25 adult patients (11 men and 14 women, average age of 47.88+/-11.16 years), and 20 healthy control subjects from the KBD areas (8 men and 12 women, average age of 47.85+/-12.05 years) and 20 from the non-KBD areas (8 men and 12 women, average age of 47.45+/-11.24 years) were also selected to serve as controls. There was no significant difference in the average age and gender distribution between the 3 groups. The serum levels of HA, TNF-alpha, VEGF, NO and Se were measured by enzyme-linked immunosorbent assay, nitrate reductase method and griphite furnace atomic absorption spectrometry. RESULTS: Serum NO level was significantly higher in KBD group (41.7+/-21.89 micromol/L) than in the health controls from KBD areas (17.1+/-13.01 micromol/L) and non-KBD areas (17.58+/-11.48 micromol/l, F=13.11, df=2, P<0.001). Serum TNF-alpha level in KBD group (32.7+/-3.55 pg/ml) was significantly higher than that in the control subjects from the non-KBD areas (30.95+/-2.22 pg/ml, F=3.672, df=2, P=0.031), but similar with the control subjects from the KBD areas (32.7+/-3.55 pg/ml). Serum TNF-alpha and NO levels were identified as the indices that differed between adult KBD patients and the controls from both KBD and non-KBD areas by differential analysis (the function of differentiation was 0.062xNO+0.173xTNF -7.218). CONCLUSION: Serum TNF-alpha and NO levels are significantly increased in adult KBD patients and are associated with the clinical manifestations of KBD.