Prothrombotic genotypes and risk of venous thromboembolism in occult cancer.

BACKGROUND: Studies have reported that the combination of some prothrombotic genotypes and overt cancer yields a synergistic effect on VTE risk. Whether individual prothrombotic genotypes or number of risk alleles in a genetic risk score (GRS) affect VTE risk in occult cancer have not been addressed. The aim of this study was to investigate the joint effect of five prothrombotic genotypes and occult cancer on VTE risk. METHODS: Cases with incident VTE (n = 1566) and a subcohort (n = 14,537) were sampled from the Scandinavian Thrombosis and Cancer Cohort (1993-2012). Five single nucleotide polymorphisms previously reported in a GRS were genotyped: ABO (rs8176719), F5 (rs6025), F2 (rs1799963), FGG (rs2066865) and F11 (rs2036914). Hazard ratios (HRs) for VTE by individual SNPs and GRS were estimated according to non-cancer and occult cancer (one year preceding a cancer diagnosis) exposure. RESULTS: Occult cancer occurred in 1817 subjects, and of these, 93 experienced a VTE. The VTE risk was 4-fold higher (HR 4.05, 95% CI 3.28-5.00) in subjects with occult cancer compared with those without cancer. Among subjects with occult cancer, those with VTE had a higher proportion of prothrombotic and advanced cancers than those without VTE. The VTE risk increased according to individual prothrombotic genotypes and GRS in cancer-free subjects, while no such effect was observed in subjects with occult cancer (HR for ≥4 versus ≤1 risk alleles in GRS: 1.14, 95% CI 0.61-2.11). CONCLUSIONS: Five well-established prothrombotic genotypes, individually or combined, were not associated with increased risk of VTE in individuals with occult cancer.

Sleep Duration and Stroke: Prospective Cohort Study and Mendelian Randomization Analysis.

BACKGROUND AND PURPOSE: Studies of sleep duration in relation to specific types of stroke are scarce. Moreover, the results are inconclusive and causality remains unclear. Our objective was to investigate whether sleep duration is associated with risk of stroke and its types using observational and Mendelian randomization designs. METHODS: The prospective study included 79 881 women and men (45-79 years of age) who were followed up for incident stroke or death over a mean follow-up of 14.6 years (1 164 646 person-years) through linkage to Swedish Registers. For the Mendelian randomization study, single-nucleotide polymorphisms associated with sleep duration were identified from a genome-wide association study. Summarized data for genetic associations with stroke were obtained from publicly available data of the MEGASTROKE and the International Stroke Genetics Consortia. RESULTS: Compared with normal sleep duration, long sleep (≥9 hours per day) was associated with increased risk of total and ischemic stroke (hazard ratios [95% CI], 1.12 [1.03-1.22] and 1.14 [1.03-1.24], respectively), whereas short sleep (<7 h/d) was linked to higher risk of intracerebral hemorrhage (hazard ratio [95% CI], 1.21 [1.03-1.41]). The 2-sample Mendelian randomization analysis supported no causal association of short or long sleep duration with ischemic stroke as a whole. CONCLUSIONS: In a prospective study, long sleep duration was associated with increased risk of total and ischemic stroke, whereas short sleep was linked to increased risk of intracerebral hemorrhage. However, the Mendelian randomization analysis did not show a significant detrimental effect of short or long sleep duration on the risk of total stroke or stroke types.

Influence of Genetic and Non-Genetic Risk Factors for Serum Uric Acid Levels and Hyperuricemia in Mexicans.

Risk of hyperuricemia is modified by genetic and environmental factors. Our aim was to identify factors associated with serum uric acid levels and hyperuricemia in Mexicans. A pilot Genome-wide association study GWAS was performed in a subgroup of participants (n = 411) from the Health Workers Cohort Study (HWCS). Single nucleotide polymorphisms (SNPs) associated with serum uric acid levels were validated in all the HWCS participants (n = 1939) and replicated in independent children (n = 1080) and adult (n = 1073) case-control studies. The meta-analysis of the whole HWCS and replication samples identified three SLC2A9 SNPs: rs1014290 (p = 2.3 × 10-64), rs3775948 (p = 8.2 × 10-64) and rs11722228 (p = 1.1 × 10-17); and an ABCG2 missense SNP, rs2231142 (p = 1.0 × 10-18). Among the non-genetic factors identified, the visceral adiposity index, smoking, the metabolic syndrome and its components (waist circumference, blood pressure, glucose and hyperlipidemia) were associated with increased serum uric acid levels and hyperuricemia (p < 0.05). Among the female HWCS participants, the odds ratio for hyperuricemia was 1.24 (95% CI, 1.01-1.53) per unit increase in soft drink consumption. As reported in other studies, our findings indicate that diet, adiposity and genetic variation contribute to the elevated prevalence of hyperuricemia in Mexico.

Serum 25-Hydroxyvitamin D Concentrations and Ischemic Stroke and Its Subtypes.

Background and Purpose- Observational studies have reported increased risk of ischemic stroke among individuals with low serum 25-hydroxyvitamin D (S-25OHD) concentrations but uncertainty remains about the causality of this association. We sought to determine whether S-25OHD concentrations are causally associated with ischemic stroke and its subtypes using Mendelian randomization. Methods- We used summary-level data for ischemic stroke (34 217 cases and 404 630 noncases) from the MEGASTROKE consortium. As instruments, we used 6 single nucleotide polymorphisms, explaining 7.5% of the variance in S-25OHD, previously identified to be associated with S-25OHD concentrations in the Study of Underlying Genetic Determinants of Vitamin D and Highly Related Traits consortium (n=79 366). The analyses were conducted using the inverse-variance-weighted method and complemented with the weighted median, heterogeneity-penalized, and Mendelian randomization-Egger approaches. Results- Genetically higher S-25OHD concentration was not associated with ischemic stroke. The odds ratios (95% CI) per genetically predicted 1-SD (≈18 nmol/L) increase in S-25OHD concentrations, based on all 6 single nucleotide polymorphisms, were 1.01 (0.94-1.08; P=0.84) for all ischemic stroke, 0.94 (0.80-1.11; P=0.49) for large artery stroke, 0.95 (0.82-1.11; P=0.55) for small vessel stroke, and 1.02 (0.90-1.16; P=0.74) for cardioembolic stroke. The results were similar in sensitivity analyses. Conclusions- These findings provide no support that higher S-25OHD concentrations are causally associated with any ischemic stroke subtype. Thus, vitamin D supplementation will unlikely reduce the risk of ischemic stroke in the general population.

An association between single nucleotide polymorphisms of Bcl-2 related anti apoptotic protein 3 gene and Keshan disease in north Chinese Han population / 中华地方病学杂志

Objective To investigate the relationship between single nucleotide polymorphisms of Bcl-2 related anti apoptotic protein 3 (BAG3) gene and Keshan disease (KD) in north Chinese Han population.Methods In 2002 a total of 285 Chinese Han subjects,including 79 KD patients and 206 control subjects were involved in this study.Genomic DNA was extracted from the peripheral venous blood sample.Blood samples were provided by the Institute of Endemic Disease Prevention,Xi'an Jiaotong University,and stored at 80 ℃.The polymorphism of genetic variation was genotyped by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF).The data was analyzed using TYPER 4.0 or SPSS16.0 software.All sample groups were tested for Hardy-Weinberg equilibrium using goodness-of-fit x2 test.Differences in genotype distribution and allele frequencies between case and control were compared by x2 test.Logistic regression analysis was applied to detect association using age as a confounding factor.Results All sample group passed the Hardy-Weinberg equilibrium test (P ＞ 0.05).Significant differences were not observed in genotype distribution between cases (rs2234962:CC,CT,TT were 0.0％,0.0％ and 100.0％,respectively;rs196295:GG,GA,AA were 22.8％,54.4％ and 22.8％,respectively;rs3858339:GG,GT,TT were 5.1％,38.0％ and 56.9％,respectively;rs3858340:TT,TC,CC were 5.1％,38.0％ and 56.9％,respectively) and controls (rs2234962:CC,CT,TT were 0.0％,1.0％ and 99.0％,respectively;rs196295:GG,GA,AA were 21.4％,51.5％ and 26.2％,respectively;rs3858339:GG,GT,TT were 5.8％,34.5％ and 59.7％,respectively;rs3858340:TT,TC,CC were 5.8％,34.5％ and 59.7％,respectively) for rs2234962,rs3858339,rs196295 and rs3858340 on BAG3 gene (x2 =0.685,0.408,0.330,0.330,P ＞ 0.05).Significant differences were not observed in genotype after agecorrecting between cases and controls for 4 SNPs on BAG3 gene (x2 =0.001,0.019,1.009,0.019,P ＞ 0.05).Conclusion The results suggest that the BAG3 gene might not be a susceptibility gene of KD in north Chinese Han population.

Study on correlation between TCF7L2 gene rs3814570 polymorphisms with T2DM in Uygur Population of Xinjiang / 重庆医学

Objective To investigate the correlation between TCF7L2 gene rs3814570 polymorphisms with type 2 diabetes mellitus(T2DM) in Uygur population of Xinjiang area.Methods By adopting the case-control study design,949 cases of T2DM were recruited as the observation group and 963 individuals Undergoing healthy physical examination were selected as the control group.The TCF7L2 gene polymorphism was detected by matrix-assisted laser desorption/ionization-time of flight(MALDI-TOF).Results The statistical differences in frequencies of CC,CT and TT genotypes and the C and T allele frequencies on TCF7L2 rs3814570 were found between the T2DM group and control group(P＜0.05).The risk of suffering from T2DM in the carriers of CT genotype was 0.331 times of that in the carriers of CC genotype(OR =0.331,95 ％ CI:0.166-0.661,P =0.002),the risk of suffering from T2DM in the carriers of TT genotype was 0.539 times of that in the carriers of CC genotype(OR=0.539,95％CI:0.348-0.834,P=0.005),and the risk of suffering from T2DM in the carriers of T allele was 0.501 times of that in the carriers of C allele(OR=0.501,95 ％ CI:0.377-0.664,P＜ 0.01).Among all subjects,the FPG level of the CT + TT genotype group on TCF7L2 gene rs3814570 locus was significantly lower than that of the CC genotype group(P＜0.05).Conclusion The rs3814570 locus in TCF7L2 gene may be associated with T2DM occurrence in Uygur population of Xinjiang area,the T allele and TT genotype might be protective factors of T2DM.

Association of genetic polymorphisms of STAT4, the cytotoxic T-lymphocyte antigen-4 and chromosome 9p21.3 with susceptibility to rheumatoid arthritis in Minnan population / 中华风湿病学杂志

Objective A very high prevalence of rheumatoid arthritis (RA) is observed in Minnan population in China.We aimed to explore the genetic characteristics of RA in Minnan population and genetic mechanisms of RA by studying the associations of three single nucleotide polymorphisms (SNPs) of signal transducer and activator of transcription 4 (STAT-4) (rs7574865),the cytotoxic T-lymphocyte antigen-4 (CTLA)-4 (rs3087243) and chromosome 9p21.3(rs1333049) with RA in Minnan population.Methods A case-control study of 119 RA patients and 125 normal controls from Quanzhou were enrolled.SNPs (rs7574865,rs3087243,rs1333049) were genotyped by allele-specific polymerase chain reaction (PCR) and analyzed by SPSS 18.0.x2-test was applied to compare allele and genotype frequeneies betweeen cases and controlsLogistic regression models were used to analyze the SNPs.Results The results showed the genotype distributions of STAT4 genes were significantly different between case and control groups (P＜0.01).Compared with the GT heterozygous genotype,TT and GG homozygosity carriers had a lower risk (OR=0498 and 0.300,P=0.018 and P=0.002 respectively).There was not statistical difference in genotypes and allele in CTLA-4 (rs3087243) between RA patients and healthy controls (x2=4.083,P=0.130),but compared with the AG genotyoe,GG homozygosity carriers had a lower risk on basis of statistics (OR=0.580,P=0.04).There was not statistical difference in genotypes and allele in the chromosome 9p21.3 (rs1333049) (P＞0.05),but compared with the GG genotype carriers,CC and GC genotypes carriers had a lower risk on basis of statistics (OR=0.565,P=0.0495).Conclusion Chromosome 9p21.3 (rs1333049) and CTLA-4 rs3087243 G/A may not be associated with susceptibility to RA in Minnan popula-tions.This replication study confirmes that STAT4 rs7574865 G/T polymorphism is associated with susceptibility to RA in Minnan population.

Association of programmed cell death-1 gene polymorphisms with chronic hepatitis C virus infection and antiviral effect / 临床肝胆病杂志

ObjectiveTo investigate the association of single nucleotide polymorphisms (SNPs) of programmed cell death-1 (PD-1) gene with chronic hepatitis C virus (HCV) infection and the effect of antiviral therapy with interferon combined with ribavirin. MethodsA total of 228 patients with chronic hepatitis C (CHC) who were hospitalized in seven hospitals in Hebei Province, China from October 2010 to October 2012 were enrolled and treated with interferon combined with ribavirin as the individualized antiviral therapy. Eighty-one persons who underwent physical examination were enrolled as control group. The TaqMan probe method was used to detect PD-1 gene polymorphisms. The distribution of alleles and genotypes at PD-1.1 and PD-1.3 were compared between the two groups, and the association between the SNPs of PD-1.1 and PD-1.3 and anti-HCV effect was analyzed. The chi-square test was used for the comparison of categorical data between groups. ResultsThe CHC group showed significantly higher frequencies of T allele and TT genotype at PD-1.1 than the control group (52.41% vs 43.21%, χ2=4.059, P=0.044; 28.51% vs 14.81%, χ2=6.469, P=0.039). The SNPs of PD-1.1 gene were not significantly associated with complete early virologic response or sustained virologic response (both P＞0.05). Both groups had CC genotype at PD-1.3. ConclusionPD-1.1 T allele might be associated with chronic HCV infection, and patients carrying TT genotype have a high risk of chronic HCV infection. PD-1.1 polymorphism is not associated with virologic response to anti-HCV therapy.

Polymorphisms in PRKCDBP, a Transcriptional Target of TNF-α, Are Associated With Inflammatory Bowel Disease in Korean.

BACKGROUND/AIMS: Emerging data indicate that polymorphic sequence variations in the tumor necrosis factor alpha (TNF-α) gene may affect its production, and be associated with the risk of inflammatory bowel disease (IBD). PRKCDBP is a putative tumor suppressor gene and a transcriptional target of TNF-α. The aim of this case-control study is to explore the possible association of single nucleotide polymorphisms (SNPs) in PRKCDBP with the development of IBD in Koreans. METHODS: Genotyping analysis of four SNPs of PRKCDBP [rs35301211 (G210A), rs11544766 (G237C), rs12294600 (C797T), and rs1051992 (T507C)] was performed on 170 ulcerative colitis (UC),131 Crohn's disease (CD) patients, and 100 unrelated healthy controls using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: Heterozygous configuration of three SNPs (G210A, G237C, and C797T) was very rare in both patients and healthy controls. However, allele frequencies of the T507C SNP showed a significant difference between UC patients and controls (P=0.037). The CC genotype of the T507C SNP was identified in 46.6% (61 of 131) of CD and 49.4% (84 of 170) of UC patients, but only in 33.0% (33 of 100) of healthy controls. Furthermore, CC homozygosity was more prevalent than TC heterozygosity in both CD and UC patients versus controls (P=0.016; gender-adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.16-4.04 and P=0.009; aOR, 2.09; 95% CI, 1.193.64; respectively). CONCLUSIONS: Our results suggest that the T507C SNP in PRKCDBP, a TNF-α-inducible gene, might be associated with susceptibility to IBD (particularly UC) development in Koreans.

Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.

BACKGROUND: The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies. METHODS AND RESULTS: We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16). CONCLUSIONS: We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.

Association between single nucleotide polymorphisms at LOXL1 promoter and Uygur patients with exfoliation syndrome / 中华实验眼科杂志

Background Exfoliation syndrome (XFS) is a systemic disease with abnormal accumulation of extracellular matrix.Researches showed that the single nucleotide polymorphisms (SNPs) of lysyl oxidase-like 1 (LOXL1) gene is associated with the pathogenesis of XFS in global population.However,the results are varied among different ethnicity and regions.Objective This study aimed to assess the association between LOXL1 gene polymorphisms and XFS in Uygur population.Methods One-hundred and fifty-two Uygur XFS patients without relativeness were enrolled from January to August in 2014,and 228 ethnicity-and gender-matched normal controls were recruited at the same period from the same region.Each individual underwent comprehensive eye examinations and 5 ml peripheral blood was collected.Genomic DNA was extracted from peripheral blood.PCR-ligase detection response (LDR) was used to determine the allele and genotype frequencies of the six SNPs rs12914489,rs4886467,rs4558370,rs4461027,rs4886761 and rs16958477 in the promoter region of LOXL1 gene.The distribution frequency between the patients and normal controls was compared by x2 test.Logistic regression analysis was used for age adjustment.This study was approved by Ethic Committe of Xinjiang Medical University,and informed consent was obtained from the subjects.Results rs12914489 site in the normal control group diverged from Hardy-Weinberg equilibrium (HWE) (P =0.033),and the rs4886467,rs4558370,rs4461027,rs4886761 and rs16958477 sites followed HWE.The frequencies of G allele and GG genotype of rs4886467 in the XFS group were lower than those in the control group (both at P =0.00) and were protective factors of XFS (OR =0.54,95 ％ CI:0.40-0.74,P =0.000;OR=0.51,95％ CI:0.33-0.78,P=0.001);the frequencies of T allele and TT genotype of rs4558370 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=1.96,95％ CI:1.23-3.11,P =0.004;OR =2.18,95％ CI:1.31-3.64,P =0.002);the frequencies of C allele and CC genotype of rs4461027 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=2.25,95％ CI:1.67-3.04,P=0.000;OR=3.06,95％ CI:1.89-4.96,P=0.000);the frequencies of T allele and TT genotype of rs4886761 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR=2.44,95％ CI:1.79-3.33,P =0.000;OR =3.02,95％ CI:1.63-5.60,P =0.000);the frequencies of C allele and CC genotype of rs16958477 in the XFS group were significantly higher than those in the control group (both at P=0.00) and were the risk factors of XFS (OR =2.00,95 ％ CI:1.47-2.71,P =0.000;OR =2.37,95 ％ CI:1.31-4.27,P =0.004).Conclusions The SNPs of promoter region of LOXL1 gene are associated with hereditary susceptibility of XFS individually in Uygur population.The SNPs of rs4886467 locus are protective factor,while the SNPs of rs4558370,rs4461027,rs4886761 and rs16958477 locus are risk factors for pathogenesis of XFS.

Association of ERα-29 gene polymorphisms with susceptibility to HBV-related hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo evaluate the relationship between estrogen receptor-α-29 (ERα-29) gene polymorphisms and the development of HBV-related hepatocellular carcinoma (HCC) in Gansu Province, China, and to investigate the pathogenesis of HCC at the gene level. MethodsGene polymorphisms of ERα-29 were analyzed in 106 HBV-related HCC patients and 98 healthy individuals as normal controls using the polymerase chain reaction-restriction fragment length polymorphism technique. Population allele frequencies were calculated using the gene counting method and then tested using the Hardy-Weinberg law of genetic equilibrium. Comparisons of genotype and allele frequencies between groups were performed using the χ2 test. ResultsThe frequencies of TT genotype and T allele of ERα-29 gene in HBV-related HCC patients were significantly higher than those in the normal controls, i.e., 31.1% and 53.8% vs. 11.2% and 32.1% (χ2 = 3.449, P＜0.05; χ2 = 3.840, P＜0.05). In contrast, the frequencies of CC genotype and C allele of ERα-29 gene in HBV-related HCC patients were significantly lower than those in the normal controls, i.e., 23.6% and 46.2% vs. 47.0% and 67.9% (χ2 = 3.488, P＜0.05; χ2 = 3.840, P＜0.05). Compared with those carrying C allele, carriers of T allele had an increased risk (2.46-fold) of HBV-related HCC (OR = 2.46, 95% CI: 1.64-3.69). Conclusion T allele of ERα-29 gene can increase the risk of HBV-related HCC.

The research of single-nucleotide polymorphisms in the PTPN22 gene conferring the susceptibility in immune thrombocytopenia / 重庆医学

Objective To investigate the single-nucleotide polymorphisms of PTPN22 gene rs2476601 ,rs3811021 and rs2488457 in patients with primary immune thrombocytopenia(ITP) .Methods Totally 100 patients with ITP and 100 cases as con-trol from Department of Hematology ,the Affiliated Baiyun Hospital of Guiyang Medical College and the Affiliated Hospital of Guiyang Medical College were collected .PTPN22 gene + 1858 loci (rs2476601) and 3′UTR region rs3811021 loci were detected by PCR-RFLP ,the promoter-1123 loci (rs2488457) were detected by PCR-SSP ,and the results were statistically analyzed .Results PTPN22 gene + 1858 locus in ITP patients and control group were all C allele ,T allele was detected ,and there was no single nucle-otide polymorphisms (R620W) exist .The frequency of PTPN22 gene rs3811021 locus TT ,CT ,CC three genotypes in ITP patients and control group had no significant difference(χ2 = 3 .686 ,P= 0 .158) .The frequency of T allele ,C allele in ITP patients and con-trol group had no significant difference(χ2 = 2 .828 ,P = 0 .093) .The frequency of PTPN22-1123 gene (rs2488457)GG ,GC ,CC three genotypes in ITP patients and control group had no significant difference(χ2 = 1 .802 ,P = 0 .406) .The frequency of C allele and G allele in ITP patients and control group had no significant difference(χ2 = 0 .003 ,P = 0 .954) .According to the gender fac-tors ,in females ,the genotype and allele frequency of SNP loci rs3811021 and rs2488457 in ITP patients and control group had no significant difference(P< 0 .05) ,so as in males(P < 0 .05) .Conclusion PTPN22 gene rs2476601 this SNP site does not exist in Guizhou Han population ,The addition of two SNP loci of PTPN22 gene (rs3811021 ,rs2488457) exists polymorphism ,but the two SNP loci has no sex difference ,the onset and ITP in Guizhou Han population had no significant correlation .

Polymorphisms in PRKCDBP, a Transcriptional Target of TNF-alpha, Are Associated With Inflammatory Bowel Disease in Korean

BACKGROUND/AIMS: Emerging data indicate that polymorphic sequence variations in the tumor necrosis factor alpha (TNF-alpha) gene may affect its production, and be associated with the risk of inflammatory bowel disease (IBD). PRKCDBP is a putative tumor suppressor gene and a transcriptional target of TNF-alpha. The aim of this case-control study is to explore the possible association of single nucleotide polymorphisms (SNPs) in PRKCDBP with the development of IBD in Koreans. METHODS: Genotyping analysis of four SNPs of PRKCDBP [rs35301211 (G210A), rs11544766 (G237C), rs12294600 (C797T), and rs1051992 (T507C)] was performed on 170 ulcerative colitis (UC),131 Crohn's disease (CD) patients, and 100 unrelated healthy controls using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: Heterozygous configuration of three SNPs (G210A, G237C, and C797T) was very rare in both patients and healthy controls. However, allele frequencies of the T507C SNP showed a significant difference between UC patients and controls (P=0.037). The CC genotype of the T507C SNP was identified in 46.6% (61 of 131) of CD and 49.4% (84 of 170) of UC patients, but only in 33.0% (33 of 100) of healthy controls. Furthermore, CC homozygosity was more prevalent than TC heterozygosity in both CD and UC patients versus controls (P=0.016; gender-adjusted odds ratio [aOR], 2.16; 95% confidence interval [CI], 1.16-4.04 and P=0.009; aOR, 2.09; 95% CI, 1.193.64; respectively) CONCLUSIONS: Our results suggest that the T507C SNP in PRKCDBP, a TNF-alpha-inducible gene, might be associated with susceptibility to IBD (particularly UC) development in Koreans.

Association of the catechol-o-methyltransferase gene polymorphisms with Korean autism spectrum disorders.

This study evaluated the family-based genetic association between autism spectrum disorders (ASDs) and 5 single-nucleotide polymorphisms (SNPs) in the catechol-o-methyltransferase gene (COMT), which was found among 151 Korean ASDs family trios (dominant model Z = 2.598, P = 0.009, P FDR = 0.045). We found a statistically significant allele transmission or association in terms of the rs6269 SNP in the ASDs trios. Moreover, in the haplotype analysis, the haplotypes with rs6269 demonstrated significant evidence of an association with ASDs (additive model rs6269-rs4818-rs4680-rs769224 haplotype P = 0.004, P FDR = 0.040). Thus, an association may exist between the variants of the COMT gene and the occurrence of ASDs in Koreans.

The relationship between frizzled 6 gene polymorphisms and neural tube defects in children of northern Han Chinese population / 中华神经科杂志

Objective To study the association of single nucleotide polymorphisms (SNPs) of the frizzled 6(FZD6) gene with neural tube defects(NTDs) in a northern Han Chinese population.Methods Three nonsynonymous SNPs in the FZD6 gene (rs827528,rs3808553,rs12549394) were examined.The SNPs were genotyped by polymerase chain reaction (PCR) and sequencing in 135 NTD patients and matched normal controls.The allele,genotype and haplotype frequencies were calculated and analyzed to examine the association between FZD6 SNPs and NTDs.Results Both T allele and TT genotype frequencies of the rs3808553 polymorphism in the NTDs group were significantly higher than those in the controls,and children with T allele and TT genotype were associated with increased risk of NTDs (OR =1.575,95％ CI 1.112-2.230,P =0.010 and OR =2.811,95％ CI 1.325-5.967,P =0.023 respectively).There were no significant differences among different genotypes or alleles in both rs827528 and rs12549394.Haplotypes AG-C and A-T-C were found associated with NTDs in the case-control study (OR =0.560,95％ CI 0.378-0.830,P=0.004 and OR=1.670,95％CI 1.126-2.475,P =0.011 respectively).Conclusions The rs3808553 polymorphism of FZD6 is obviously associated with NTDs in children of northern Han Chinese population.The TT genotype may increase the risk for NTDs.The rs827528 and rs12549394 polymorphisms of FZD6 may have no association with NTDs.

Clinical study of warfarin anticoagulation effect in elderly patients based on vitamin K epoxide reductase complex 1 and cytochrome P450 2C9 genetic polymorphisms / 中华老年医学杂志

Objective To investigate the efficacy and safety of warfarin anticoagulation in Chinese elderly patients based on vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genetic polymorphisms.Methods Clinical data of 41 elderly patients with initial anticoagulation therapy in our emergency department and respiratory department were collected.Patients were divided into observation group (n=20,patients treated with warfarin based on genetic polymorphisms) and control group (n =21,patients treated based on clinical experience).The international normalized ratio (INR),the time of INR stabilized within target range (2.0-3.0) and the incidence of bleeding episodes in 6-month follow up were compared between groups.Results INR within target range at day 3,4,5 and 7 were 0.0％,42.1％,52.6％,68.4％ in observation group and 0.0％,10.0％,25.0％,35.0％ in control group,respectively.There were significant differences in INR within target range at day 4,7 between the two groups (both P＜0.05),while no significant difference was found in INR within target range at day 5 (P＞0.05).The time of INR stabilized within target range was shorter in observation group than in control group [(9.5±2.4) d vs.(12.3± 4.8) d,P＜0.05].Bleeding complication occurred in 3 patients in observation group and 5 patients in control group,and there was no significant difference between the two groups.Conclusions Warfarin therapy based on VKORC1 and CYP2C9 gene polymorphisms may shorten the time of first INR reaching the target value and INR within target range in elderly patients.However,the risk of bleeding complications should be alerted.

Gene polymorphisms in the nucleotide excision repair pathway and lung cancer susceptibility / 国际肿瘤学杂志

Nucleotide excision repair (NER) pathway is one of the principal ways of the repair of DNA damage.The single nucleotide polymorphisms (SNP) of its key genes such as xeroderma pigmentosum group A (XPA) gene,excision repair cross complementingl (ERCC1) gene and xeroderma pigmentosum group D (XPD) gene may be associated with differences in the DNA repair capacity and may influence an individual's risk of lung cancer,because the variant genotype in those polymorphisms might destroy or alter repair function.

Correlation analysis of B cell activating factor promotor polymorphism-871 C/T and systemic lupus erythematosus / 中华风湿病学杂志

Objective The study was aimed to detect the correlation of B cell activating factor (BAFF) promotor polymorphism-871 C/T and systemic lupus erythematosus (SLE).Methods BAFF promotor polymorphism-871 C/T was detected by the means of allele specific polymerase chain reaction (ASPCR) and agarose gel electrophoresis in 76 cases of SLE and 80 nonthrombosis normal individuals.The data of genotypic frequency and allele genotypic frequency were analyzed statistically with x2 test between the two groups.Results Fifty-one point two percent of normal individuals exhibited C/C.Thirty-five percent were heterozygous for C/T,and 13.8％ were homozygous for T/T.SLE group exhibited a different distribution pattern (30.3％ C/C,43.4％C/T,26.3％T/T).The allele frequency of T in SLE and normal individuals was 48.0％ and 31.2％ respectively.There was significant difference in the BAFF-871 C/T genotypic frequency between the SLE and nonthrombosis normal individuals (P＜0.05).Conclusion The polymorphism-871 C/T of BAFF promoter is correlated with the pathogenesis of SLE.The gene may be a major susceptible gene for SLE in Chinses Han people.Further investigations may be needed.