广西地区人群IL-6及IL-10单核苷酸多态性与HBV相关肝癌关联研究

目的 探讨广西地区人群IL-6和IL-10基因单核苷酸多态性(SNP)与HBV相关肝癌的关系.方法 采用以医院为基础的病例对照研究方法,以381例肝癌患者为病例组,340例HBsAg携带者及359例健康体检者为对照组.应用荧光定量PCR对IL-6基因-572位点,IL-10基因-819和-592位点进行基因分型.采用非条件logistic回归模型分析比较携带不同基因型人群罹患肝癌的风险.结果 IL-6基因-572位点G/C等位基因在病例组、HBsAg携带组及健康对照组中分布差异有统计学意义(P＜0.05),与CC基因型相比,携带GG基因型个体慢性HBV感染危险性增加(OR=2.171,95%CI:1.068-4.415).IL-10基因-819位点T/C等位基因在三组的分布差异有统计学意义(P＜0.05),与CC基因型相比,携带TT基因型健康个体罹患肝癌的危险性增加(OR=2.791,95%CI:1.326～5.874).携带TT基因型的HBsAg携带者罹患肝癌的风险也增加(OR=3.522,95%CI:1.707～7.266).IL-10基因-592位点A/C等位基因在三组中的分布差异无统计学意义(P＞0.05),与CC基因型相比,携带AA基因型健康个体罹患肝癌的危险性降低(OR=0.389,95%CI:0.173-0.875),携带AA基因型的HBsAg携带者肝癌的罹患风险也降低(OR=0.336,95%CI:0.154-0.734).结论 IL-6基因-572位点SNP与广西地区人群慢性HBV感染有关,IL-10基因-819位点TT基因型个体罹患肝癌的风险增加,IL-592位点从基因型个体罹患肝癌的风险降低.

Abstract：

Objective To investigate the association between single nucleotide polymorphisms (SNPs)in cytokine IL-6, IL- 10 genes and HBV-related hepatocellular carcinoma(HCC). Methods A hospital-based case-control study was conducted in 381 cases with HBV-related HCC, 340 HBsAg carriers and 359 non-tumor controls. Genotypes of-572 site of IL-6 gene and-819, -592 sites of IL-10 gene were determined by real-time polymorphism chain reaction. Unconditional logistic regression was used to estimate the odds ratios(ORs)and 95 confidence intervals(C/s). Results For the G/C alleles of -572 loci on IL-6 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, GG genotype increased the risk of HBV infection (OR=2.171,95% Ch 1.068-4.415), but did not seem to be associated with HCC. For the alleles of-819 and -592 site of IL-10 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, TT genotype increased the risks of both HCC(OR=2.791,95%CI:1.326-5.874), and HCC in HBsAg carriers(0R=3.522,95%CI: 1.707-7.266). When compared with CC genotype on -592 site, the AA genotype reduced the risk of both HCC(OR=0.389, 95% CI:0.173-0.875), and HCC in HBsAg carriers(OR=0.336, 95% CI: 0.154-0.734). Conclusion The SNPs in -572 site of IL-6 gone might be associated with the risk of HBV infection. The SNPs in -819 site of IL-10 gene increased the risk of HCC, but -592 site of IL-10 gene decreased the risk of HCC.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

广西地区人群IL-6及IL-10单核苷酸多态性与HBV相关肝癌关联研究

Objective To investigate the association between single nucleotide polymorphisms (SNPs)in cytokine IL-6, IL- 10 genes and HBV-related hepatocellular carcinoma(HCC). Methods A hospital-based case-control study was conducted in 381 cases with HBV-related HCC, 340 HBsAg carriers and 359 non-tumor controls. Genotypes of-572 site of IL-6 gene and-819, -592 sites of IL-10 gene were determined by real-time polymorphism chain reaction. Unconditional logistic regression was used to estimate the odds ratios(ORs)and 95 confidence intervals(C/s). Results For the G/C alleles of -572 loci on IL-6 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, GG genotype increased the risk of HBV infection (OR=2.171,95% Ch 1.068-4.415), but did not seem to be associated with HCC. For the alleles of-819 and -592 site of IL-10 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, TT genotype increased the risks of both HCC(OR=2.791,95%CI:1.326-5.874), and HCC in HBsAg carriers(0R=3.522,95%CI: 1.707-7.266). When compared with CC genotype on -592 site, the AA genotype reduced the risk of both HCC(OR=0.389, 95% CI:0.173-0.875), and HCC in HBsAg carriers(OR=0.336, 95% CI: 0.154-0.734). Conclusion The SNPs in -572 site of IL-6 gone might be associated with the risk of HBV infection. The SNPs in -819 site of IL-10 gene increased the risk of HCC, but -592 site of IL-10 gene decreased the risk of HCC.     

广西地区人群IL-6及IL-10单核苷酸多态性与HBV相关肝癌关联研究

Objective To investigate the association between single nucleotide polymorphisms (SNPs)in cytokine IL-6, IL- 10 genes and HBV-related hepatocellular carcinoma(HCC). Methods A hospital-based case-control study was conducted in 381 cases with HBV-related HCC, 340 HBsAg carriers and 359 non-tumor controls. Genotypes of-572 site of IL-6 gene and-819, -592 sites of IL-10 gene were determined by real-time polymorphism chain reaction. Unconditional logistic regression was used to estimate the odds ratios(ORs)and 95 confidence intervals(C/s). Results For the G/C alleles of -572 loci on IL-6 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, GG genotype increased the risk of HBV infection (OR=2.171,95% Ch 1.068-4.415), but did not seem to be associated with HCC. For the alleles of-819 and -592 site of IL-10 gene, there were significant differences between the three groups(P＜0.05). Compared with CC genotype, TT genotype increased the risks of both HCC(OR=2.791,95%CI:1.326-5.874), and HCC in HBsAg carriers(0R=3.522,95%CI: 1.707-7.266). When compared with CC genotype on -592 site, the AA genotype reduced the risk of both HCC(OR=0.389, 95% CI:0.173-0.875), and HCC in HBsAg carriers(OR=0.336, 95% CI: 0.154-0.734). Conclusion The SNPs in -572 site of IL-6 gone might be associated with the risk of HBV infection. The SNPs in -819 site of IL-10 gene increased the risk of HCC, but -592 site of IL-10 gene decreased the risk of HCC.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

甲型H1N1流行性感冒病毒血凝素蛋白基因进化研究

Objective To determine the evolutionary rate and divergence time of influenza A virus HA gene isolated recently worldwide pandemic and explore the origin and its transmission. Methods A total of 344 HI sequences available in the GenBank (including 248 isolated from human, 84 from swine, 11 from avian, and 1 from ferret) and 7 isolated in Shanghai were collected. The nucleotide substitution rate and time to most recent common ancestor (tMRCA) was calculated using molecular clock theory and Bayesian Skyline Plot (BSP) based on Markov chain Monte Carlo. Then genetic phylogeny was constructed referring to posterior distribution. Results It was found that H1 sequences in the US from human, swine and avian were clustered significantly with swine H1 ones from Asia phylogenetieally (Cluster US). The second cluster (Cluster Eurasian Human) nearly consisted of human H1 sequences isolated in other regions. The third cluster (Cluster Eurasian Animal) consisted of swine and avian H1 sequences from China and Italy respectively. As for all the H1 sequences, the evolutionary rate was of 2.57×10-3substitutions/site per year averagely (95% Highest Posterior Density: 1.96×10-3-3.03×10-3/site per year). The estimated dates for tMRCA of human H1 in Europe and swine H1 in the mainland of China were the earliest, with the corresponding rates of 6.46×10-3/site per year and 0.97×10-3/site per year respectively. The tMRCAs of human and swine H1 sequences from the US were similar, with the rates of 5.86×10-3/site per year and 5.02×10-3/site per year. Conclusion The present flu outbreak was possibly induced by long-term circulation of influenza A virus (H1 N1) in human population and swine herds in America. There was no evidence proving that influenza virus in China involved in the present outbreak.     

Association between SLC11A1 polymorphisms and susceptibility to different clinical forms of tuberculosis in the Peruvian population.

Polymorphism in SLC11A1 has been implicated in host susceptibility to tuberculosis. We have studied associations between INT4, D543N, and 3'UTR polymorphisms of SLC11A1 and different clinical forms of TB. Analysis used 507 patients with pulmonary TB, 123 with extra pulmonary TB and 513 controls. INT4 and D543N showed allelic association with pulmonary TB (P=0.02 and 0.03 respectively). INT4-D543N-3'UTR haplotypes showed an association with pulmonary TB (P=0.03). No association of SLC11A1 with miliary TB was observed, and a possible association of D543N to the pleural form (P=0.08) was suggested. These results support association between SLC11A1 and TB, particularly to the common pulmonary form.     

NRAMP1基因INT4和3’UTR位点多态性与肺结核易感性的研究

目的 探讨人类自然抵抗相关巨噬细胞蛋白1（NRAMP1）基因INT4和3＇UTR位点多态性与中国北方汉族成人肺结核发病的关系.方法 采用1：1配对的病例对照研究设计,用聚合酶链反应-限制性片段长度多态性分析方法检测NRAMP1基因中INT4和3＇UTR两个多态性位点,对与肺结核相关的危险因素进行问卷调查,进行单因素和多因素条件logistic回归分析,同时对基因型与肺结核病变的性质和程度进行研究.结果 对124对研究对象进行了INT4和3＇UTR两个多态性位点的基因分型,3＇UTR TGTG＋/del基因型病例组频率显著高于对照组,粗OR值（95%CI）为2.923（1.557～5.487）.病例组和对照组INT4各基因型频率比较差异均无统计学意义.对17个环境危险因素进行了单因素分析,在多因素分析中调整卡痕、体重指数、人均居住面积、家族史4个因素后,3＇UTR TGTG＋/del基因型仍与肺结核显著相关,调整OR值（95%CI）为2.955（1.369～6.381）.在INT4不同基因型中,病例组和对照组肺结核病变性质差异具有统计学意义（x2=9.634,P＜0.05）.结论 NRAMP1基因3＇UTR位点多态性可能是中国北方汉族成人肺结核的易感因素,而INT4多态性可能与肺结核的病变性质有关系.     

东亚人群NRAMP1基因多态性与结核易感性的Meta分析

目的应用Meta分析探讨东亚人群NRAMP1基因3个多态性位点与结核易感性的关系。方法应用主题词和关键词“NRAMP1”、“SLC11A1”、“tuberculosis”和“结核”,检索1995年1月至2005年5月Medline、Ovid及CBMdisc数据库发表的有关文献,并辅以文献追溯的方法。结果结核病组和对照组3’UTR、D543N和INT4位点的多态现象同最常见纯合子基因型频率比值比（OR）的合并OR值分别为1．68（95％CI：1．31～2．16,P〈0．001）;178（95％CI：1,38～2．30,P〈0．001）;1．56（95％CI：0．72～3．35,P=0．26）。Egger线性回归分析提示3’UTR和D543N基因型相关文献没有发表偏倚,INT4基因型相关文献有一定的出版偏倚。结论东亚人群NRAMPl基因3’UTR和D543N多态性位点与结核易感性相关;INT4多态性位点与结核易感性无统计学意义。     

Novel insight in the association between salmonellosis or campylobacteriosis and chronic illness, and the role of host genetics in susceptibility to these diseases

We studied the role of host genetics in the susceptibility to severe Salmonella and Campylobacter infections and chronic sequelae of these infections. Participants of a previous case-control study were sent a buccal swab kit and a questionnaire about occurrence of chronic sequelae. Single nucleotide polymorphisms (SNPs) in the TLR4 (rs4986790), IFNG (rs2430561 and rs1861493), STAT1 (rs1914408), IL1B (rs16944), NRAMP (SLC11A1 rs2276631), JUN (rs11688) and VDR (rs10735810) genes were determined. In total, 687 controls, 457 Campylobacter cases and 193 Salmonella cases participated. None of the SNPs were associated with Campylobacter or Salmonella infections. None of the participants developed Guillain-Barré, Miller-Fisher or Reiter's syndrome. Reactive arthritis occurred in 5% and 2% of cases and controls, respectively. Campylobacter cases more frequently experienced gastroenteritis episodes than controls. Campylobacter or Salmonella infection in women, use of proton pump inhibitors and an SNP in the IFNG gene were independent risk factors for reactive arthritis. Another SNP in the IFNG gene and use of proton pump inhibitors were risk factors for recurrent episodes of gastroenteritis. In conclusion, reactive arthritis and recurrent gastroenteritis episodes are common after infection and host genetic factors play a role in susceptibility to these long-term health effects.     

自然抗性相关巨噬细胞蛋白1基因多态性与肺结核易感性的研究

目的　探讨自然抗性相关巨噬细胞蛋白 1基因 (NRAMP1)多态性与中国汉族人群肺结核发病的关系。方法　采用以医院为基础的病例对照研究设计 ,用聚合酶链反应 限制性片段长度多态性分析 (PCR RFLP)法检测NRAMP1基因中INT4、D5 4 3N及 3′UTR 3个多态性位点的基因型 ,并对结核病相关危险因素进行问卷调查 ,应用SPSS软件进行单因素和多因素非条件logistic回归分析。2 0 0 1年 4月至 2 0 0 2年 6月选择 110例肺结核病例 ,平均年龄为 (2 8± 13)岁 ;对照组为 180名健康体检者 ,平均年龄为 (2 7± 9)岁。对NRAMP1基因各多态性位点进行单因素分析。结果　病例组D5 4 3NG/A及 3′UTRTGTG +/del基因型频率显著高于对照组 ,OR值 (95 %CI)分别为 2 2 2 (1 0 3～ 4 78)和 1 93(1 14～ 3 2 6 )。病例组和对照INT4各基因型频率比较差异无显著性。多因素分析调整暴露史和疫苗接种史 2个因素后 ,D5 4 3NG/A及 3′UTRTGTG +/del基因型仍与结核病显著相关 ,调整OR值 (95 %CI)分别为 3 0 4 (1 12～ 8 2 7)和 2 36 (1 2 0～ 4 6 4 ) ,而病例和对照组INT4位点多态性比较差异未见显著性。结论　NRAMP1基因D5 4 3N及 3′UTR位点多态性可能是汉族人群肺结核的易感因素。     

MBL基因H/L、P/Q位点多态性与新疆维吾尔族结核病的相关性研究

目的探讨MBL基因H/L、P/Q位点的多态性是否与新疆维吾尔族人群结核病发病相关。方法通过使用引物序列特异性PCR（PCR-SSP）的方法分别对226例新疆维吾尔族活动性肺结核患者及231例有结核分枝杆菌接触史的新疆维吾尔族健康者研究MBL基因的H/L、P/Q多态性位点与新疆维吾尔族人群结核病易感性的关系。结果新疆维吾尔族结核病例组中MBL-H/L突变基因型频率与新疆维吾尔族健康对照组突变基因型频率分别为25.66%、18.18%,差异无统计学意义（OR=1.600,95%CI：1.020～2.511,P=0.040,Pc=0.052〉0.05）。新疆维吾尔族结核病例组中MBL-P/Q突变基因型频率与新疆维吾尔族健康对照组突变基因型频率分别为10.62%、10.82%,差异无统计学意义（OR=0.979,95%CI：0.541~1.797,P=0.050,Pc=0.994〉0.05）。MBL-AB等位基因型与MBL-HL等位基因在病例组的相交系数为0.018,P值为0.006〈0.05。新疆维吾尔族人群MBL-A/B,H/L,P/Q之间测出4个单倍体型：HPA,LPA,LPB,LQA。结论新疆维吾尔族人群中MBL基因H/L、P/Q多态性与结核病易感性无明显相关性。新疆维吾尔族人群MBL-A/B,H/L,P/Q等位基因型之间存在连锁不平衡,MBL-A/B等位基因型与MBL-H/L等位基因有正向交互作用。     

Vitamin D and tuberculosis

Tuberculosis is highly prevalent worldwide, accounting for nearly two million deaths annually. Vitamin D influences the immune response to tuberculosis, and vitamin D deficiency has been associated with increased tuberculosis risk in different populations. Genetic variability may influence host susceptibility to developing active tuberculosis and treatment response. Studies examining the association between genetic polymorphisms, particularly the gene coding for the vitamin D receptor (VDR), and TB susceptibility and treatment response are inconclusive. However, sufficient evidence is available to warrant larger epidemiologic studies that should aim to identify possible interactions between VDR polymorphisms and vitamin D status.     

MBL2 gene polymorphisms and susceptibility to tuberculosis in a northeastern Brazilian population

The innate immune system represents the first line of host defense against pathogens. Genetics factors regulating the immune responses play a role in the susceptibility to infectious diseases, such as tuberculosis (TB). We analyzed MBL2 promoter and exon 1 functional single nucleotide polymorphisms (SNPs) in a group of 155 TB patients and 148 healthy controls in order to evaluate their influence on the onset of infection and TB development. There was no association between MBL2 −550 HL promoter polymorphisms and susceptibility to develop TB, but heterozygous −221 Y/X genotype was significantly more frequent in pulmonary TB patients than controls. Moreover, MBL2 exon 1 O allele, was significantly associated with susceptibility to TB development in general (p = 0.023, OR = 1.61, 95% CI 1.05–2.49) and pulmonary TB (p = 0.0008, OR = 2.16, 95% CI 1.35–3.46); C allele at codon 57, as well as A/C genotype, were significantly more frequent in TB patients than in controls. Our results indicate that MBL2 polymorphisms, especially at codon 57, could be considered as risk factors for TB development.     

SLC22A12基因rs893006和SLC2A9基因rs11942223位点与高尿酸血症关联性研究

目的 探讨rs893006和rs11942223位点与高尿酸血症的关系,为高尿酸血症的群体遗传学研究以及防治提供依据。方法 在某体检机构确定364例高尿酸血症患者为病例组,按性别、民族、年龄进行1:1匹配,选择364例健康个体为对照组,采用Sequenom Mass ARRAY iPLEX GOLD技术检测两组中单核苷酸多态性,通过多因子降维法（multifactor dimensionality reduction,MDR）分析基因位点和体质指数（body mass index,BMI）的交互作用。结果 病例组的肌酐、总胆固醇、甘油三酯、收缩压和BMI较对照组高,差异均有统计学意义（均有P<0.05）。在男性中,rs893006位点基因型频率和等位基因频率在两组中的差异均有统计学意义（χ₁2=6.372,P=0.041;χ₂2=4.935,P=0.026）;在男性不同遗传模型中,rs893006位点的G等位基因为保护因素,携带GG+GT基因型发生高尿酸血症的风险是TT基因型的0.405倍。采用MDR分析表明:BMI和rs893006及rs11942223位点之间可能存在较弱的协同作用,rs893006和rs11942223位点可能存在明显的拮抗作用,携带高危基因型群体发生高尿酸血症的风险是低危基因型群体的1.99倍（χ2=12.499,P<0.001）。结论 rs893006位点基因的多态性与男性高尿酸血症的发病有关联,位点rs893006和rs11942223与BMI之间存在交互作用。     

Clusters of Drug-Resistant Mycobacterium tuberculosis Detected by Whole-Genome Sequence Analysis of Nationwide Sample,Thailand, 2014–2017

Multidrug-resistant tuberculosis (MDR TB), pre-extensively drug-resistant tuberculosis (pre-XDR TB), and extensively drug-resistant tuberculosis (XDR TB) complicate disease control. We analyzed whole-genome sequence data for 579 phenotypically drug-resistant M. tuberculosis isolates (28% of available MDR/pre-XDR and all culturable XDR TB isolates collected in Thailand during 2014–2017). Most isolates were from lineage 2 (n = 482; 83.2%). Cluster analysis revealed that 281/579 isolates (48.5%) formed 89 clusters, including 205 MDR TB, 46 pre-XDR TB, 19 XDR TB, and 11 poly–drug-resistant TB isolates based on genotypic drug resistance. Members of most clusters had the same subset of drug resistance-associated mutations, supporting potential primary resistance in MDR TB (n = 176/205; 85.9%), pre-XDR TB (n = 29/46; 63.0%), and XDR TB (n = 14/19; 73.7%). Thirteen major clades were significantly associated with geography (p<0.001). Clusters of clonal origin contribute greatly to the high prevalence of drug-resistant TB in Thailand.