Contribution of the P2X7 1513A/C loss-of-function polymorphism to extrapulmonary tuberculosis susceptibility in Tunisian populations

The P2X7 receptor has been found to be linked to an increased risk for tuberculosis in some populations. In this study, we investigate whether the P2X7 receptor plays a role in increasing susceptibility to tuberculosis in Tunisia. We examined two 1513A/C and -762T/C polymorphisms at the P2X7 receptor in 168 patients with pulmonary TB (pTB), 55 patients with extrapulmonary TB (epTB) and 150 blood donors from Tunisia. Genotyping of 1513A/C and -762T/C polymorphisms was performed in purified genomic DNA using PCR-restriction fragment length polymorphism and allele-specific PCR, respectively. The 1513C, CC and AC loss-of-function allele and genotypes were overrepresented in the epTB group compared with the control group (45% vs. 17%, P=10(-8) ; 24% vs. 4%, P=3 × 10(-7) ; 42% vs. 27%, P=10(-3) , respectively). Additionally, they were associated with 3.83-, 11.86- and 3.15-fold risks of developing this clinical tuberculosis form, respectively. No associations between the -762T/C polymorphism and tuberculosis disease, as well as disease anatomic location were observed. Collectively, our results suggest that the P2X7 1513A/C loss-of-function polymorphism may contribute to susceptibility to epTB in Tunisian populations.     

A 5' intronic splice site polymorphism leads to a null allele of the P2X7 gene in 1-2% of the Caucasian population

The P2X(7) gene is important for the innate immune response but known polymorphisms do not explain all subjects with loss of P2X(7) function. A splice site mutation (g-->t) was found at position +1 of the first intron of the P2X(7) gene in 7 of 336 Caucasians and 1 of 39 subjects of Indian ethnicity. All eight subjects were heterozygous for the uncommon 1513A-->C polymorphism of the P2X(7) gene. RT-PCR and sequencing showed the splice site mutation was on the 1513C allele in the Caucasians and on the 1513A allele in the Indian subject. The splice site mutation is an inherited polymorphism and gives rise to a P2X(7) null allele in 1-2% of the Caucasian population.     

CISH基因多态性与结核病易感性的相关性研究

目的:寻找肺结核的易感位点,探索宿主遗传因素差异对肺结核发病的影响,为肺结核的预防和药物研发提供理论依据。方法:对1218名汉族居民进行病例对照研究,其中病例组600例,对照组618例,进行流行病学调查和生化指标检查。运用限制性片段长度多态性聚合酶链反应(PCR-RFLP)技术检测CISH基因rs2239751和rs622502的基因型分布,探讨CISH基因多态性与中国汉族人群肺结核易感性的关联性。结果:CISH基因的rs2239751和rs622502等位基因分布均符合Hardy-Weinberg(H-W)遗传平衡定律(P0.05)。rs2239751位点基因型和等位基因分布在两组间差异有统计学意义,P值分别为0.013和0.01,并且携带C等位基因个体患肺结核的风险是携带A等位基因的个体1.16倍(95%CI=1.03-1.29,P=0.01)。rs2239751基因分型结果在女性病例组和对照组中差异有统计学意义,P值为0.007,OR(95%CI)为1.51(1.12-2.03)。rs2239751基因分型结果在45岁人群病例组和对照组中差异有统计学意义,P值为0.010,OR(95%CI)为1.32(1.07-1.64)。rs622502位点基因型和等位基因分布在两组间差异均无统计学意义(P0.05)。结论:在汉族人群中,rs2239751位点多态性可能是肺结核的危险因素之一,C等位基因为风险等位基因。rs2239751基因多态性与肺结核的关联性仅限于于女性和45岁人群。rs622502位点多态性可能与肺结核无关。     

Relationship between single nucleotide polymorphism of interleukin-18 and susceptibility to pulmonary tuberculosis in the Chinese Han population

Interleukin-18 (IL-18) is a multi-functional cytokine capable of inducing either Th1 or Th2 polarization depending on the immunologic milieu. IL-18 may influence the host response to Mycobacterium tuberculosis (M.tb) infection. To investigate the relationship between single nucleotide polymorphisms of the IL-18 and susceptibility to pulmonary tuberculosis in the Chinese Han population, the IL-18 gene was sequenced to detect polymorphisms and to examine the genotype frequencies in 300 patients and 702 healthy controls. DNA sequencing revealed three IL-18 variants: rs1946518, rs5744247, and rs549908. It also revealed that allele A of rs1946518 confers a 1.47-fold increased risk of developing tuberculosis (TB) (P = 0.0001, OR [95%CI] = 1.47 [1.21-1.78]), and that the C allele of rs5744247 confers a 0.77-fold decreased risk of disease (P = 0.01, R [95%CI] = 0.77 [0.632-0.937]). The genotypes rs1946518, rs5744247 and rs549908 were found to be significantly associated with TB. Estimation of the frequencies of haplotypes revealed a potential risk haplotype AGA (P = 0.01, OR [95%CI] = 1.41 [1.15-1.72]) and a protective haplotype CCA (P = 0.01, OR [95%CI] = 0.70 [0.57-0.85]) for TB. The present findings suggest that polymorphisms in the IL-18 gene may affect susceptibility to TB and increase the risk of developing the disease in the Chinese Han population.     

Association of β-fibrinogen gene -148C/T and -455G/A polymorphisms and coronary artery disease in Chinese population: A Meta analysis

The purpose of our study was to evaluate the correlation between the b-fibrinogen gene –148C/T and –455G/A polymorphisms and susceptibility to coronary artery disease in the Chinese population using a meta–analytic approach. Eligible studies about this correlation were identified by searching the PubMed, EMBASE, and CNKI databases. Of the 13 identified, 7 (with 1488 cases and 1234 controls) involved the –148C/T polymorphism and 9 (with 1023 cases and 1081 controls) involved the –455G/A polymorphism. No publication bias was detectable and heterogeneity testing found significant differ-ences between the ORs for both groups of studies. The combined OR for the 7 studies on susceptibility to coronary artery disease in –148T allele carriers compared to the –148C/C wild-type homozygotes was 1.31 (95%CI: 0.94－1.84, P=0.11). The combined OR for the 9 studies on susceptibility to coronary artery disease in –455A allele carriers compared to the –455G/G wild-type homozygotes was 1.75 (95%CI: 1.24－2.46, P=0.001). Our results suggest the absence of an association between the b-fibrinogen gene –148C/T polymorphism and susceptibility to coronary artery disease and the possibility that –455G/A polymorphism (in particular, allele A) increases susceptibility to this disease in the Chinese population.     

Association between the −159C/T CD14 gene polymorphism and tuberculosis in a Korean population

The aim of the present study was to confirm the association between the CD14 −159C/T polymorphism and tuberculosis in the Korean population and to elucidate the functional basis for this putative association. CD14 −159C/T genotypes were determined by PCR – restriction fragment length polymorphism analysis in 274 tuberculosis patients and 422 healthy controls. Recombinant CD14 promoter–luciferase reporter constructs, including the −159T or −159C allele, were transfected into K562 and BEAS-2B cells, and luciferase activities were measured and compared. Levels of serum sCD14 and interferon-γ secreted by peripheral blood mononuclear cells (PBMCs) were measured using enzyme-linked immunosorbent assay.The frequency of −159TT genotypes was higher in tuberculosis patients than in healthy controls. The promoter activity of the −159T allele was higher than that of the −159C allele. Serum sCD14 levels were higher among tuberculosis patients with −159TT genotypes than among those with −159CC genotypes and interferon-γ release by PBMCs was decreased in subjects with −159TT genotypes. In conclusion, the −159TT CD14 genotypes were associated with tuberculosis development in Koreans. This association might be a result of the higher promoter activity of the −159T allele, the higher level of sCD14, and the decreased interferon-γ secretion in subjects with −159TT genotypes.     

Association of tuberculosis and polymorphisms in the promoter region of macrophage migration inhibitory factor (MIF) in a Southwestern China Han population

The macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that plays an important role in the pathogenesis of immune diseases. High levels of MIF have been detected in the sera of patients with tuberculosis (TB), and it has been proposed that MIF gene polymorphisms may influence the risk of developing TB. The aim of this study was to evaluate the potential relationship between functional polymorphisms of MIF and TB in a Han population from Southwestern China. TB patients (n=215) and healthy unrelated controls (n=245) were recruited for this study. Genomic DNA was isolated from all the participants. The MIF-173 G/C SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The MIF-794 CATT(5-8) microsatellite was evaluated by direct sequencing of the subsequent PCR products. Association analysis of the two polymorphisms showed that the frequency of -173 (GC+CC) in TB patients and controls was 49.3% and 31.4%, respectively, which was statistically significant (OR=2.12, 95% CI=1.45-3.10, P<0.001); the frequencies of -794 (7/X+8/X) were 56.7% and 45.3%, respectively, also statistically significant between the TB and healthy controls (OR=1.58, 95% CI=1.10-2.29, P=0.015). In summary, Genetic variation in the MIF gene is closely associated with tuberculosis. Both the 173 (GC+CC) SNP and -794 (7/X+8/X) microsatellite increased the risk of Chinese Han developing TB.     

葡萄糖转运体9（GLUT9）基因启动子区的rs13124007（G/C）及rs6850166（G/A）位点的单核苷酸多态性（SNP）与汉族女性痛风相关性研究（英文）

目的：探讨葡萄糖转运体9（GLUT9）基因启动子区的rs13124007（C/G）及rs6850166（A/G）位点的单核苷酸多态性（SNP）与中国汉族女性人群痛风易感性之间的相关性。方法：选取185例痛风患者和300例正常对照者,提取基因组DNA,采用聚合酶链式反应（PCR技术）,特异性扩增GLUT9基因所需要的目的片段,对扩增的目的片段进行测序后,比较痛风组和正常对照组的基因型频率及等位基因频率分布情况。结果：女性痛风组中GLUT9基因的启动子区rs13124007和rs6805116两个位点的基因型频率分布与正常对照组相比,统计学上无明显的差异（X2=0.906,P=0.636;X2=3.335,P=0.189）,rs13124007 SNP位点的C等位基因频率和rs6850166SNP位点的A的等位基因频率与正常对照组相比也无明显的统计学差异（X2=0.506,P=0.477;X2=3.268,P=0.071）。结论：葡萄糖转运体9（GLUT9）基因启动子区的rs13124007（C/G）及rs6850166（A/G）位点的单核苷酸多态性（SNP）与中国汉族女性人群痛风易感性无明显的相关性。     

A Meta-Analysis of P2X7 Gene-762T/C Polymorphism and Pulmonary Tuberculosis Susceptibility

AimWe performed a comprehensive meta-analysis to determine the association between P2X7 -762T/C polymorphism and pulmonary tuberculosis susceptibility.MethodologyBased on comprehensive searches of the PubMed, SCI, Elsevier, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between P2X7 -762T/C polymorphism and pulmonary tuberculosis risk. Pooled odds ratio (ORs) and 95% confidence intervals (95%CIs) were calculated in random-effects model.ResultsA total of 2207 tuberculosis cases and 2220 controls in 8 case-control studies were included in this meta-analysis. Allele model (C vs. T: p = 0.15; OR = 0.83, 95% CI = 0.65–1.07), homozygous model (CC vs. TT: p = 0.23; OR = 0.73, 95% CI = 0.44 to 1.22), and heterozygous model (CT vs. TT: p = 0.57; OR = 0.92, 95% CI = 0.68 to 1.24) did not show increased risk of developing pulmonary tuberculosis. Similarly, dominant model (CC+CT vs. TT: p = 0.32; OR = 0.84, 95% CI = 0.59 to 1.19) and recessive model (CC vs. CT+TT: p = 0.08; OR = 0.77, 95% CI = 0.57 to 1.04) failed to show increased risk of developing pulmonary tuberculosis. Subgroup analysis by ethnicity did not detect any significant association between P2X7–762T/C polymorphism and pulmonary tuberculosis susceptibility.ConclusionsP2X7 -762T/C gene polymorphism is not associated with pulmonary tuberculosis susceptibility.     

Association of TIRAP (MAL) gene polymorhisms with susceptibility to tuberculosis in a Chinese population

Toll-interleukin 1 receptor (TIR) domain containing adaptor protein (TIRAP; also known as MAL) is an essential adaptor molecule in Toll-like receptor signaling, involved in activating the innate immune response during infection. Genetic variations in the TIRAP gene may influence human susceptibility to infectious disease. To date, in the Chinese population, a possible predisposition of TIRAP gene variants to tuberculosis has not been reported. We investigated whether TIRAP gene polymorphisms are associated with the development of tuberculosis in a Chinese population. We investigated all the single-nucleotide polymorphisms (SNPs) within the TIRAP exon 5 in a case-control study of 212 patients with tuberculosis and 215 controls in a Chinese population. Genotyping was performed to identify the polymorphisms of TIRAP gene by PCR-DNA sequencing method. Haplotypes for the TIRAP gene variants were constructed using Haplo view version 4.2. Six polymorphisms of the SNPs listed in the National Center for Biotechnology Information database were detected in these Chinese tuberculosis patients. It was found that both the frequency of the 286A allele (odds ratio (OR) = 13.37; 95% confidence interval (CI) = 0.75-238.3; P < 0.01) and the frequency of 286AG genotype (OR = 13.57; 95%CI = 0.76-242.5; P < 0.01) were significantly higher in patients than in healthy controls. However, two other SNPs, C539T and C558T, reported to be associated with tuberculosis in other populations, were found not to be associated with tuberculosis in this Chinese population. We conclude that TIRAP G286A (D96N) polymorphism is associated with susceptibility to tuberculosis and may be a new risk factor for the development of tuberculosis in China.     

Polymorphic allele of human MRC1 confer protection against tuberculosis in a Chinese population

Mannose receptor is a member of the C-type lectin receptor family involved in pathogen molecular-pattern recognition, and plays a critical role in shaping host immune response. Single nucleotide polymorphisms (SNPs) in the MRC1 gene may affect expression levels and differences in the structure and function of proteins in different individuals, thereby affecting individual susceptibility to pulmonary tuberculosis. However, to date, MRC1 polymorphisms associated with susceptibility to pulmonary tuberculosis have not yet been reported. The present study aimed to investigate potential associations of SNPs in the MRC1 gene with pulmonary tuberculosis in a Chinese population. Six SNPs (G1186A, G1195A, T1212C, C1221G, C1303T and C1323T) in exon 7 of the MRC1 gene were genotyped using the PCR and DNA sequencing methods in the pulmonary tuberculosis patients and the healthy controls. Linkage disequilibrium analysis was performed between polymorphic sites. The study found that the allele frequency of G1186A (rs34039386) of the MRC1 gene in a Chinese population was higher in the pulmonary tuberculosis group than the healthy control group. There was a significant difference in frequency distribution between the two groups (P = 0.037; OR = 0.76; 95% CI, 0.58-0.98). Genotypic analysis also indicated that the AG genotypes in a Chinese population were significantly correlated with pulmonary tuberculosis (P < 0.01; OR = 0.57; 95% CI, 0.37-0.87). After adjustment for age and gender, G1186A sites were found to be dominant (P < 0.01; OR = 0.59; 95% CI, 0.40-0.87), over-dominant (P = 0.045; OR = 0.69; 95% CI, 0.47-0.99) and additive models (P = 0.041; OR = 0.76; 95% CI, 0.59-0.99) in association with pulmonary tuberculosis. But, no association was found between the other 5 SNPs (G1195A, T1212C, C1221G, C1303T and C1323T) and tuberculosis (P > 0.05). This study is the first to report that genetic variants in the MRC1 gene can be associated with pulmonary tuberculosis in a Chinese population, and may reduce the risk of infecting pulmonary tuberculosis. This also provides a new experimental basis to clarify the pathogenesis of pulmonary tuberculosis.     

BMP2 variants in the risk of ankylosing spondylitis

The purpose of the study was to explore the genetic effects of bone morphogenetic protein (BMP2) polymorphisms on the susceptibility to ankylosing spondylitis (AS) in Chinese Han population. The case-control study included 120 AS cases and 110 healthy controls. Hardy-Weinberg equilibrium test was performed in control group. BMP2 rs235768 and rs3178250 polymorphisms were analyzed by polymerase chain reaction and direct sequencing. Additionally, the χ² test was used to estimate association strength between BMP2 genetic polymorphisms and AS susceptibility, and the results were assessed via odds ratio (OR) with the corresponding 95% confidence interval (95%CI). Results adjustment was performed using logistic regression analysis. AA, AT, TT genotype and A, T allele frequencies of BMP2 rs235768 polymorphism presented no significant differences between case and control groups (P > .05 for all). TC genotype of rs3178250 polymorphism showed significantly higher in case group than that in control group (P = .048). After adjusting, TC genotype was a risk factor for AS (OR = 2.095; 95%CI = 1.086-4.038; P = .027). BMP2 rs3178250 polymorphism may increase individual susceptibility to AS in Chinese Han population.     

Association of -619C/T polymorphism in CDSN gene and psoriasis risk: a meta-analysis

Previous studies investigating the association between corneodesmosin (CDSN) polymorphisms and psoriasis risk have provided inconsistent results. The aim of our study was to clarify the effects of CDSN -619C/T polymorphism on psoriasis risk by conducting a meta-analysis. We conducted searches of the published literature in Pubmed and Embase databases up to October 2010. Six studies with a total of 842 psoriasis cases and 981 healthy controls were retrieved. Statistical analysis was performed with the programs Review Manager (version 5.0.24) and Stata (version 9.2). Meta-analysis results showed that there was no significant difference in CDSN -619C/T genotype distribution between psoriasis and control in the comparisons of C allele vs T allele, CC vs CT + TT, CC + CT vs TT, CC vs TT, and CC vs CT (respectively: OR = 1.28, 95%CI = 0.82-2.00, P = 0.28; OR = 1.33, 95%CI = 0.80-2.21, P = 0.28; OR = 1.23, 95%CI = 0.80-1.91, P = 0.35; OR = 1.41, 95%CI = 0.64-3.12, P = 0.40; OR = 1.30, 95%CI = 0.81-2.06, P = 0.27). In the subgroup analysis by ethnicity, results also showed no significant association between CDSN -619C/T polymorphism and susceptibility to psoriasis in both Caucasian and Asian populations. In conclusion, this meta-analysis suggests that CDSN -619C/T polymorphism may not be associated with susceptibility to psoriasis.     

CTLA-4 exon 1 +49 polymorphism alone and in a haplotype with ?318 promoter polymorphism may confer susceptibility to chronic HBV infection in Chinese Han patients

Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) plays a pivotal role in regulating T cell activation, which is believably critical for the outcome of hepatitis B virus (HBV) infection. The expression and function of CTLA-4 may be affected by gene polymorphisms. This study investigated the influence of CTLA-4 polymorphisms on disease susceptibility in Chinese Han patients with chronic HBV infection. CTLA-4 +49A/G and -318C/T polymorphisms were evaluated by DNA amplification with polymerase chain reaction followed by the restriction fragment length polymorphism analysis. The patients with chronic HBV infection had higher frequencies of genotype AA and allele A of CTLA-4 +49A/G polymorphism. The haplotype +49A-318C was significantly over-represented (P < 0.001) and haplotype +49G-318C under-represented (P = 0.006) in the patients. The +49GG genotype was more frequent (P = 0.009) and +49A allele was less frequent in patients with lower ALT levels (P = 0.012) in HBeAg positive chronic hepatitis B. It is indicated that CTLA-4 +49A/G polymorphism alone and in a haplotype with -318C allele may confer susceptibility to chronic HBV infection in Chinese Han patients.     

IL-22基因多态性与中国人群肺结核易感性的相关性研究

本研究旨在探讨白细胞介素22(interleukin 22,IL-22)基因多态性位点与肺结核易感性的关系。采用SNPscan™多重单核苷酸多态性(single nucleotide polymorphism,SNP)分型技术,对453例肺结核患者(结核病组)和373例与患者长期密切接触者〔包括109例潜伏结核感染(latent tuberculosis infection,LTBI)者、264例健康对照者〕的IL-22基因的4个SNP位点(rs1179249、rs2227491、rs17224704、rs2227478)多态性进行分析。结核病组、LTBI组和对照组中4个SNP位点的基因型分布经哈温平衡(Hardy-Weinberg equilibrium,HWE)检验均处于遗传平衡状态。结果显示,rs17224704位点存在AA、TA和TT基因型。＞55岁人群中,此位点TA基因型在对照组中的分布显著高于结核病组(P＝0.047 9,OR＝0.365,95% CI＝0.135～0.991);AA基因型在LTBI组中的分布显著低于结核病组(P＝0.027 6);TA基因型在LTBI组中的分布显著高于结核病组(P＝0.007 37,OR＝0.213,95% CI＝0.069～0.660)。对照组和LTBI组的等位基因T频率显著高于结核病组(P＝0.026 9,OR＝0.388,95% CI＝0.167～0.897;P＝0.025 0,OR＝0.322,95% CI＝0.119～0.867)。IL-22基因rs17224704的多态性可能与中国重庆地区汉族人群肺结核易感性显著相关,其等位基因T可能是肺结核的保护基因。     

Genetic polymorphisms in TNFA/TNFR2 genes and Chagas disease in a Colombian endemic population

In this study we investigated the association of functional single nucleotide polymorphisms of tumor necrosis factor-alfa (TNFA) and TNF receptor 2 (TNFR2) genes in determining the susceptibility to Chagas' disease. This study included 313 patients from Colombia serologically positive for Trypanosoma cruzi antigens (cardiomyopathic, N=159; asymptomatic, N=154). Genotypes were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism method. We found a significant difference in the distribution of the TNFA -1031C (p=0.0153, OR=1.69, CI=1.10-2.58) and -308A (p=0.0002, OR=2.60, CI=1.53-4.39) alleles between cardiomyopathic and asymptomatic subjects. In addition, we observed that the TNFR2 +676T allele was monomorphic in our population. Our results suggest that TNFA -1031C and -308A gene polymorphisms may influence the susceptibility to develop chagasic cardiomyopathy in the population under study.     

DDAH2启动子区-1150C/A多态性与中国汉族人群冠心病的遗传易感性研究

目的:研究DDAH2启动子区-1150 C/A rs805304多态性与中国汉族人群冠心病之间的相关性。方法:应用限制性片段长度多态性聚合酶链反应(PCR-RFLP)的分析方法,对381例冠心病患者和629例健康人群中DDAH2基因A-1150C rs805304多态进行基因分型。结果:病例组和对照组A-1150C rs805304位点基因型分布均符合Hardy-Wenberg平衡;两组间A-1150C位点基因型间无显著性的差异(P=0.34);病例组和对照组A-1150C位点的等位频率分布也无显著的差别,但是在冠心病病例中,A等位频率有低于C等位频率的趋势(P=0.069)。结论:DDAH2启动子区-1150 C/A rs805304多态性与中国汉族人群冠心病的发病不相关。     

Fibroblast growth factor receptor 4 polymorphisms and coronary artery disease: a case control study

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in vascular system. FGFR4 rs351855 (Gly388Arg) polymorphism has shown to be a risk factor for many diseases. The aim of this study was to investigate the association between FGFR4 polymorphisms and the susceptibility to coronary artery disease (CAD) in the Chinese population. We identified three polymorphisms in the FGFR4 gene, rs351855G/A (Gly388Arg), rs145302848C/G and rs147603016G/A, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 658 CAD cases and 692 healthy controls. Results showed that frequencies of GA genotype, AA genotype and A allele in rs351855 (Gly388Arg) polymorphism were significantly lower in CAD patients than in controls [odds ratio (OR) = 0.79, 95 % confidence intervals (CI) 0.62-0.99, P = 0.042; OR = 0.58, 95 % CI 0.41-0.81, P = 0.002; and OR = 0.77, 95 % CI 0.66-0.90, P = 0.001, respectively]. The rs147603016GA genotype and A allele also showed lower numbers in CAD cases (OR = 0.58, 95 % CI 0.36-0.93, P = 0.025; and OR = 0.59, 95 % CI 0.40-0.95, P = 0.028). The rs145302848C/G polymorphism did not show any correlation with CAD. Haplotype analysis revealed that the prevalence of ACG haplotype (rs351855, rs145302848 and rs147603016) was significantly decreased in CAD patients (P = 0.002). Our data suggested that the FGFR4 rs351855G/A (Gly388Arg) and rs147603016G/A polymorphisms could act as protective factors against CAD in the Chinese population and indicated that a single gene polymorphism could have diverse functions in different diseases.     

The prevalence of CD33 and MS4A6A variant in Chinese Han population with Alzheimer's disease

CD33 and MS4A6A genes play potential key roles in the pathogenesis of Alzheimer's disease (AD). One recent genome-wide association study has revealed that the rs3865444 polymorphism in the CD33 gene and rs610932 polymorphism in the MS4A6A gene are associated with susceptibility to AD in Caucasians. To evaluate the relationship between the polymorphism of the CD33, MS4A6A gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 383, age > 54) to determine the prevalence of single-nucleotide polymorphism of two genes in patients with AD in Chinese population of Mainland, and clarified whether these polymorphisms are risk factors for AD. The prevalence of the allele (T) in the rs3865444 polymorphism of the CD33 gene and allele (C) in rs610932 polymorphism of the MS4A6A gene was significantly different in AD patients and control subjects (P < 0.001, respectively), and the results were not influenced by age, gender, or APOE status. Our data revealed the allele (T) of the rs3865444 polymorphism of the CD33 gene and the allele (C) of the rs610932 polymorphism of the MS4A6A gene may contribute to AD risk in the Chinese Han population.     

Influence of interleukin-12 receptor β1 polymorphisms on tuberculosis

Host genetic factors may be important determinants of susceptibility to tuberculosis, and several candidate gene polymorphisms have been shown to date. A series of recent reports concerning rare human deficiencies in the type-1 cytokine pathway suggest that more subtle variants of relevant genes may also contribute to susceptibility to tuberculosis at the general population level. To investigate whether polymorphisms in the interleukin-12 receptor (IL-12R) gene predispose individuals to tuberculosis, we studied these genes by single-strand conformational polymorphism analysis and direct sequencing. Although no common polymorphisms could be identified in the IL-12R beta 2 gene ( IL-12RB2), we confirmed four single nucleotide polymorphisms (SNPs; 641A-->G, 684C-->T, 1094T-->C, and 1132G-->C) causing three missense variants (Q214R, M365T, G378R) and one synonymous substitution in the extracellular domain of the IL-12R beta 1 gene ( IL12RB1). All SNPs were in almost perfect linkage disequilibrium (D'=0.98), and two common haplotypes of IL12RB1(allele 1: Q214-M365-G378; allele 2: R214-T365-R378) were revealed. Polymerase chain reaction/restriction fragment length polymorphism and sequence analyses were used to type IL12RB1polymorphisms in 98 patients with tuberculosis and 197 healthy controls in Japanese populations. In our case-control association study of tuberculosis, the R214-T365-R378 allele (allele 2) was over-represented in patients with tuberculosis, and homozygosity for R214-T365-R378 (the 2/2 genotype) was significantly associated with tuberculosis (odds ratio: 2.45; 95% CI: 1.20-4.99; P=0.013). In healthy subjects, homozygotes for R214-T365-R378 had lower levels of IL-12-induced signaling, according to differences in cellular responses to IL-12 between two haplotypes. These data suggest that the R214-T365-R378 allele, i.e., variation in IL12RB1, contribute to tuberculosis susceptibility in the Japanese population. This genetic variation may predispose individuals to tuberculosis infection by diminishing receptor responsiveness to IL-12 and to IL-23, leading to partial dysfunction of interferon-gamma-mediated immunity.