基质金属蛋白酶9基因-1562C/T多态性与新疆维吾尔族心肌梗死的相关性研究

目的 探讨新疆维吾尔族人群基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)基因启动子区-1562C/T多态性与心肌梗死(myocardialinfarction,MI)发病的相关性.方法 选择经皮冠状动脉造影检查确诊的维吾尔族心肌梗死患者347例(MI组),以同期冠脉造影阴性、排除冠心病诊断的403例维吾尔族患者为对照组.采用聚合酶链反应-限制性片段长度多态性方法对所有纳入对象MMP9基因-1562C/T多态性进行分析,比较两组间MMP9基因多态性频率分布的差异,并结合造影情况,探讨MMP9基因多态性与MI发病及冠脉狭窄程度的关系.结果 MI组CT+TT基因型频率(27.67%)明显高于对照组(14.14%),两组差异具有统计学意义(χ2=20.99,P＜0.01),T等位基因频率在MI组和对照组分别为15.71%、7.56%(χ2=24.57,P＜0.01).Logistic回归分析显示,携带-1562T等位基因的个体发生MI的风险大约升高2倍(OR=2.009,95%CI:1.250～3.230);携带T等位基因合并糖尿病的个体发生MI的风险明显升高(OR=3.714,95%CI:1.299～10.773).MMP9基因-1562C/T多态性分布与MI冠脉狭窄程度差异无统计学意义.结论 MMP9基因-1562C/T多态性可能与新疆维吾尔族人群MI茇病具有相关性;-1562T等位基因可能是MI遗传易感性的基因标记之一;-1562T等位基因与糖尿病在MI发生中具有协同作用.MMP9基因-1562C/T多态性与MI冠脉狭窄程度无关.

Abstract：

Objective To investigate the association between matrix metalloproteinase 9 gene (MMP9)- 1562C/T polymorphism and myocardial infarction (MI) in Uighur population of Xinjiang.Methods A total of 347 patients with MI evidenced by coronary arteriography, and 403 controls free from coronary artery disease with normal angiograms were recruited for the study. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) was used to detect the -1562C/T functional promoter polymorphism of the MMP9 gene. The relationship between the polymorphism and the severity of coronary arterial stenosis was analyzed. Results The results showed that the frequency of CT and TT genotypes in patients with MI (27. 67%) was significantly higher than that in controls (14. 14%). The frequencies of the - 1562T allele were 15. 71% and 7. 56% in the MI group and the control group respectively (2 = 24.57, P＜0.01). Logistic regression analysis indicated that the T allele carriers (CT+TT) had significantly increased risk of MI compared with the CC carriers (OR=2. 009, 95%CI: 1. 250-3. 230). Individuals carrying the -1562T allele with diabetes mellitus were at an increased risk of MI (OR=3. 714, 95% CI: 1. 299-10. 773). The frequencies of CT and TT genotypes were not significantly different among MI patients with one, two and three or more significantly diseased vessels (χ2 =0. 491, P=0. 782). Conclusion The - 1562C/T polymorphism in the MMP9 gene promoter is associated with the susceptibility to MI in the Uighur population of Xinjiang. The T allele might be a risk factor of MI. And there was a coordinated effect between the -1562T allele and diabetes mellitus in the development of MI.The -1562C/T polymorphism may not be a predictor of the severity of coronary atherosclerosis.     

Endothelial nitric oxide synthase gene polymorphisms and prostate cancer risk in Serbian population

Genome-wide association studies (GWAS) have identified over 46 SNPs associated with human prostate cancer (PCa). Some studies have shown correlation of the nitric oxide synthase (NOS) NOS3 gene polymorphisms with the risk and/or progression of PCa. This study aimed to evaluate the association of NOS3 gene polymorphisms (−786T>C, −764A>G, −714G>T, −690C>T, −649G>A and 894G>T) with PCa risk and progression. 150 patients with PCa, 150 patients with BPH and 100 age-matched healthy controls were recruited in this study. Genotyping of promoter polymorphisms was performed by bi-directional DNA sequencing, and for 894G>T by RFLP analysis. There was no significant association between the alleles and genotypes of these genetic variants and PCa risk. For −786T>C polymorphism, we found that C allele is associated with absence of metastases, assuming dominant genetic model (P = 0.049; OR, 0.50; 95% CI, 0.25–1.00). It was found that, compared with NOS3 −690C>T variant CC genotype, CT and TT genotypes confer decreased risk of developing metastases (dominant model, P = 0.015, OR, 0.24; 95% CI, 0.07–0.88) and show association with low clinical tumour stage, compared with stages T₃ and T₄ (dominant model, P = 0.046, OR, 0.20; 95% CI, 0.04–1.02). Genetic variants −764A>G, −714G>T, −649G>A were not detected in our study group. There is evidence of an inverse correlation of the NOS3 894G>T minor allele with high serum PSA (>20 ng/ml) (dominant model, P = 0.013, OR, 0.37; 95% CI, 0.17–0.82). Our results suggest that NOS3 gene polymorphisms are genetic susceptibility factors for the progression of PCa and patient outcome.     

Meta-analysis of three polymorphisms in the steroid-5-alpha-reductase, alpha polypeptide 2 gene (SRD5A2) and risk of prostate cancer

The steroid-5-alpha-reductase, alpha polypeptide 2 (SRD5A2) gene plays a crucial role in androgen metabolism pathway in human prostate. It encodes SRD5A2 enzyme, which catalyses testosterone to dihydrotestosterone (DHT). DHT is the main active structure binding with androgen receptor (AR). After the activation of AR, it further regulates a series of target genes in androgen metabolism pathway. However, no clear consensus has been reached on the association between the SRD5A2 V89L, A49T and TA repeat polymorphisms and prostate cancer (PCa) risk. Thus, we performed a meta-analysis of 31 association studies with 14,726 PCa cases and 15,802 controls. We found no association between PCa and 89L compared with 89V allele [odds ratio (OR) = 1.02, 95% confidence interval (CI) 0.98-1.06, P(heterogeneity) = 0.44]. The 49T allele showed a significantly elevated effect on the high stage (Stages III-IV) of PCa risk both under the dominant genetic model (OR = 2.13, 95% CI 1.44-3.15, P(heterogeneity) = 0.65) and in the contrast T versus A allele (OR = 2.06, 95% CI 1.41-3.02, P(heterogeneity) = 0.69). There was a significantly decreased association between PCa and long TA repeat as compared versus short TA repeat (OR = 0.86, 95% CI 0.74-1.00, P(heterogeneity) = 0.79). No significant between-study heterogeneity was found in all subjects under four genetic models (dominant model, recessive model, allele comparison and homozygosity comparison) for these three polymorphisms, respectively, so the fixed effects model was used to pool the result. Our result indicated that carriers of 49T might improve the risk of PCa in higher stages (Stages III-IV), carriers of long TA repeat might decrease the risk of PCa and 89L may not be an important risk factor for PCa. However, due to the limited sample sizes, this meta-analysis did not achieve sufficiently conclusive results. Still more well-designed studies should be performed to clarify the role of these three polymorphisms in the development of PCa.     

Genetic variation in transforming growth factor-beta1 gene associated with increased risk of esophageal squamous cell carcinoma

The genetic alterations leading to esophageal squamous cell carcinoma (ESCC) are gradually being discovered. A wide variety of genes have been associated with ESCC development as well as tumor progression. Transforming growth factor-beta1 (TGF-beta1) is a multifunctional cytokine; it promotes tumor growth and metastasis in later stages of of cancer development. Variations in the DNA sequence in the TGF-beta1 gene may lead to altered TGF-beta1 production and/or activity, and so this can modulate an individual's susceptibility to ESCC. To test this hypothesis, we investigated the association of the TGF-beta1 gene -509 C/T and 869 T/C (Leu10Pro) polymorphisms and their haplotypes with the risk of ESCC. 247 patients with ESCC and 260 age- and sex-matched controls were studied using a polymerase chain reaction-restriction fragment length polymorphism. There were significant differences in the genotype and allele distribution of 869 T/C polymorphism of the TGF-beta1 gene among cases and controls. The 869 TC and CC genotypes were associated with a significantly increased risk of ESCC as compared with the 869 TT genotypes [odds ratio (OR) = 1.882, 95% confidence interval (CI) 1.212-2.923, P = 0.005 and OR = 2.099, 95% CI 1.288-3.421, P = 0.003, respectively]. Consistent with the results of the genotyping analyses, the -509 T/869 C haplotype was associated with a significantly increased risk of ESCC as compared with the -509 C/869 T haplotype (OR = 1.463; 95% CI 1.120-1.912; P = 0.005). This study shows for the first time that TGF-beta1 gene 869 T/C polymorphism may contribute to a genetic risk factor for ESCC in a Chinese population.     

Association of fibronectin Msp iv polymorphism and diabetic nephropathy susceptibility in Chinese Han population

Aim: Our study was aimed to study the distributional characteristics of fibronectin (Fn) Msp iv polymorphism in Chinese Han Population and investigate its association with susceptibility and clinicopathologic features of diabetic nephropathy (DN). Methods: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were applied to testify Fn Msp iv genotypes among 108 patients with DN and 86 healthy individuals. Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of Fn Msp iv polymorphism and onset risk and clinicopathologic stages of DN. Results: The comparison of genotype and allele distribution in normal, micro and massive proteinuria groups showed that genotype and allele distribution in massive proteinuria group showed great differences, compared with those of control group (P = 0.006, P = 0.004). Further analysis on the association of Fn Msp iv polymorphism and occurrence of abnormal proteinuria suggested that DD genotype and D allele appeared to be a risk factor for abnormal proteinuria (OR = 3.553, 95% CI = 1.278-9.875; OR = 2.442, 95% CI = 1.378-4.327). Then, we analyzed the effects of Fn Msp iv polymorphism on the clinicopathologic stages of DN, the result showed that DD genotype showed great effect on the occurrence of early-onset DN (OR = 7.500, 95% CI = 1.691-33.272). For the DN patients with D allele, the risk for early-onset DN was increased 3.445 folds (OR = 4.445, 95% CI = 1.869-33.10.574). Conclusion: Fn Msp iv polymorphism appeared to be associated with DN susceptibility.     

A pilot study of the association of manganese superoxide dismutase and glutathione peroxidase 1 single gene polymorphisms with prostate cancer and serum prostate specific antigen levels

Introduction

The aim of the study was to evaluate the potential association of single gene polymorphisms of the antioxidant enzymes manganese superoxide dismutase (MnSOD) and glutathione peroxidase (GPX1) with prostate cancer (PCa).

Material and methods

Manganese superoxide dismutase and glutathione peroxidase 1 genotypes and allele frequencies in 49 prostate cancer cases (PCa group) and 98 control subjects were determined. Analysis of genotypes in control group individuals were performed in two subgroups according to serum prostate-specific antigen levels: the control group (n = 49), with prostate specific antigen (PSA) level < 4 ng/ml; and the nonPCa-high PSA control group (n = 49), with serum PSA > 4 ng/ml. Determination of MnSOD Ala-9Val and GPX1 Pro198Leu polymorphisms was performed using real-time polymerase chain reaction amplification.

Results

No association was found between GPX1 polymorphisms and PCa in all groups (p > 0.05). In the PCa group, the frequency of homozygote Val allele carriers was significantly higher in comparison to nonPCa-high PSA control cases. Therefore, Val/Val genotype was found significantly suspicious for PCa risk (OR = 2.48; 95% CI: 1.37–4.48; p = 0.002). Furthermore, an overall protective effect of the Ala allele of the MnSOD polymorphism on PCa risk was detected. These findings in this small Turkish population suggested that individual risk of PCa may be modulated by MnSOD polymorphism especially in patients with high PSA, but GPX1 polymorphism seemed to have no effect on PCa risk.

Conclusions

The presence of genetic variants of antioxidant enzymes could have a potential influence on genesis of prostatic malignancy.     

Anti- and proinflammatory cytokine gene polymorphism and genetic predisposition: association with smoking, tumor stage and grade, and bacillus Calmette-Guérin immunotherapy in bladder cancer

Cytokines mediate many immune and inflammatory responses contributing to tumorigenesis. The present study evaluated polymorphisms of IL4, IL6, and TNF (previously TNFA) genes influencing risk in development of transitional cell carcinoma of bladder and recurrence after bacillus Calmette-Guérin (BCG) immunotherapy. The study included 136 unrelated histopathologically confirmed cases and 200 population-based controls. Genomic DNA was extracted from peripheral leukocytes and genotyped for polymorphism in IL4 intron 3, with point mutations identified by amplification refractory mutation system polymerase chain reaction (ARMS-PCR) in IL6-174 G/C and by PCR-restriction fragment length polymorphism analysis in TNF-308 G/A. The IL6 variant C/C exhibited significant association with bladder cancer risk (odds ratio OR = 2.811, P = 0.004), but IL4 and TNF genetic variants did not. Significant association was observed for IL4 (B1/B2+B2/B2) with high-grade or late-stage tumor for TaG3+T1 and T2+ (OR = 5.950, and 6.342 respectively) and with smoking (P = 0.004, OR = 4.202). Low recurrence risk was observed in BCG-treated patients carrying C/C genotype of IL6 (hazard ratio = 0.298, P = 0.03), and also higher recurrence-free survival (log rank P = 0.021). TNF and IL4 demonstrated no association of bladder cancer risk and BCG therapy. The low-producing variant C/C of IL6 may be a risk factor for bladder cancer, whereas high-producing genotypes of IL4 (B1/B2+B2/B2) may predispose to higher risk in patients with high-grade or late-stage tumor and smoking habits. The low-producing C/C IL6 genotype, which favors Th1 response, may be a beneficial prognostic indicator for treatment and survival of BCG-treated patients.     

食管癌发病风险与NAD(P)H:醌氧化还原酶1C609T基因多态性

目的 研究NAD(P)H：醌氧化还原酶l[NAD(P)H：quinone oxidoreductase l，NQO1]C609T基因多态性与食管鳞状上皮癌(esophageal squamous cell carcinoma，ESCC)发病风险的关系。方法 应用聚合酶链反应-限制性片段长度多态性方法检测193例ESCC患者及141名正常对照的NQOl C609T多态性位点的基因型。结果 ESCC患者的突变型(T)等位基因频率明显高于健康对照组(X^2=4．86，P=0．028)。ESCC患者的NQO1C／C和C／T基因型频率与健康对照组相比差异无显著性(X^2值分别为2．27和0．127；P值分别为0．132和0．721)，而ESCC患者的T／T基因型频率明显高于对照组(X^2=4．39，P=0．036)。与NQOlC／C及C／T基因型相比，T／T基因型可明显增加患ESCC的风险性(校正OR=1．8l，95％CI：1．04～3．15)，且在有上消化道肿瘤家族史的患者中尤为明显(校正OR=2．22，95％CI：1．18～4．17)。结论 对NQO1 C609T多态性位点的基因型检测可能对判断ESCC高危个体具有指导意义。     

The role of genetic variants of matrix metalloproteinases in coronary and carotid atherosclerosis

Current evidence suggests that matrix metalloproteinases (MMPs) have a role in early atherosclerosis, plaque rupture and myocardial infarction. Polymorphisms in MMP genes have been examined for associations with atherosclerosis, but interpretation is complicated by methodological issues. This article presents a systematic review of these association studies and a meta-analysis of available data for polymorphisms where a sufficient number of studies was available. The 5A allele of the MMP3 5A/6A polymorphism was associated with acute myocardial infarction (odds ratio (OR) 1.26, 95% confidence interval (CI) 1.1 to 1.4, p<0.001), suggesting its role in plaque rupture. There was no association with the functional MMP9 -1562C/T polymorphism (OR 1.11, 95% CI 1.0 to 1.3, p = 0.18). Current data provide evidence for the role of MMP3 polymorphism in plaque destabilisation, but elucidation of the role of other MMP gene variants in atherosclerosis will depend on better study design, including a larger sample size, extensive screening of individual genes with haplotype analysis and replication of studies to avoid publication bias.     

Roles of genetic variants in the PI3K/PTEN pathways in susceptibility to colorectal carcinoma and clinical outcomes treated with FOLFOX regimen

The genetic or abnormal activation of PI3K/PTEN signaling pathway play an important role with regard to disease progression in variety of human malignancies. Experimental and epidemiologic studies indicated that the genetic polymorphisms in the PTEN, PI3K genes are associated with cancer risk, yet little evidence exists for those 2 genes and colorectal cancer (CRC) risk. To address this, we evaluated whether PTEN rs701848, PIK3CA rs2699887 variants are associated with CRC susceptibility, clinicopathological parameters and clinical outcomes in CRC patients treated with FOLFOX (Oxaliplatin, Leucovorin, 5-Fluorouracil) regimen. A case-control study was performed in 780 CRC patients and 764 healthy controls using the TaqMan assay method. A significant increased risk of CRC was observed in patients carrying PTEN rs701848 TC or CC genotype (adjusted OR=1.306, 95% CI=1.030-1.655, P=0.027; adjusted OR=1.543, 95% CI=1.148-2.075, P=0.004, respectively), TC/CC genotype (adjusted OR=1.367, 95% CI=1.090-1.714, P=0.043) in the dominant model, and C allele (adjusted OR=1.229, 95% CI=1.067-1.416, P=0.004). However, no association was detected between rs2699887 in the PIK3CA gene and CRC risk. A significant association was found between pathological grade (Dukes A and B vs. Dukes C and D) and PIK3CA rs2699887 genotypes. Furthermore, Kaplan-Meier analysis revealed that PTEN rs701848 genotypes were significantly associated with the overall survival (OS) of CRC patients treated with FOLFOX regimen (n=780). Individuals carrying PTEN rs701848 TC or TC/CC genotypes showed significantly longer median survival time (MST) than TT genotype and significant hazard ratio (TC: adjusted HR=0.523, 95% CI=0.325-0.840, P=0.007; TC/CC: adjusted HR=0.545, 95% CI=0.351-0.845, P=0.007). Therefore, rs701848 polymorphism in the PTEN gene is associated with susceptibility to CRC, and C allele of rs701848 showed significant independent better prognosis of CRC patients treated with FOLFOX regimen. These results indicate that rs701848 in the PTEN gene might be a candidate pharmacogenomic factor to assess the susceptibility and prognosis in CRC patients.     

Effect of matrix metalloproteinase‐21 (572C/T) polymorphism on HIV‐associated neurocognitive disorder

Remodeling of extracellular matrix (ECM) by matrix metalloproteinases (MMPs) is a presumed reason for the development of HIV‐associated neurocognitive disorders (HAND). The coding region polymorphism in MMP‐21 572C/T gene may have a potential functional effect on ECM remodeling. Hence, we aimed to examine the association of MMP‐21 polymorphism with the modulation of HAND severity and its prevalence in HIV‐infected and healthy individuals. Genotyping of MMP‐21 572C/T polymorphism was performed by PCR‐RFLP in total 150 HIV‐infected individuals, 50 with HAND, 100 without HAND and 150 healthy controls. MMP‐21 572TT genotype was predominantly higher in HAND patients compared with no HAND (OR = 1.63, p = 0.57). MMP‐21 572T allele was associated with reduce risk for HAND severity (OR = 0.50, p = 0.04). Similarly, MMP‐21 572TT genotype underrepresented in HIV‐infected individuals compared to healthy controls (3.0% vs 6.7%, OR = 0.27, p = 0.08). MMP‐21 572CT genotype and early HIV disease stage showed a higher risk for the advancement of HIV disease with marginal significance (OR = 1.89, p = 0.07). MMP‐21 572CT genotype increased the risk for the modulation of HAND severity in tobacco users (OR = 1.98, p = 0.43). MMP‐21 572CT genotype among tobacco and alcohol users showed elevated risk for the development of HAND in HIV‐infected individuals (OR = 2.30, p = 0.15; OR = 1.86, p = 0.23). Similarly, MMP‐21 572TT genotype enhanced the risk for the development of HAND in tobacco users (OR = 3.48, p = 0.40). In conclusion, the presence of coding region 572T allele may have protection for HAND severity. MMP‐21 572C/T polymorphism and tobacco and alcohol usage may facilitate the development of HAND.     

135G>C and 172G>T polymorphism in the 5' untranslated region of RAD51 and sporadic endometrial cancer risk in Polish women

BACKGROUND : Despite advanced diagnostic and therapeutic procedures, endometrial cancer (EC) is still responsible for high morbidity and mortality of women. The genetic variability in RAD51 may contribute to the appearance and progression of various cancers including EC. AIM : We investigated the association of polymorphisms in the DNA repair genes RAD51 135G>C and 172G>T with endometrial cancer risk. MATERIAL AND METHODS : The genotypes of RAD51 135G>C and 172G>T polymorphism were determined by PCR-RFLP methods in endometrial tissue of 240 cancer subjects and 240 healthy subjects who served as controls. RESULTS : In the present work we demonstrated a significant positive association between the RAD51 C/C genotype and endometrial carcinoma, with an adjusted odds ratio (OR) of 13.0 (p < 0.0001). The distribution of genotypes for 135G>C SNP in endometrial cancer patients vs. controls was: 10% vs. 27% for GG, 13% vs. 58% for GC and 77% vs. 15% for CC genotype, respectively. Variant 135C allele of RAD51 increased the cancer risk (OR = 1.81; 95% CI 0.11-2.93, p = 0.022). The higher risk of EC occurrence was associated with the combined C135C-G172T genotype (OR = 7.69; 95% CI 3.45-17.12). CONCLUSION : The results indicated that the polymorphism 135G>C of the RAD51 gene may be positively associated with endometrial carcinoma in the Polish population. Further studies, conducted on a larger group, are required to clarify this point.     

Steroid hormone genotypes ARStuI and ER325 are linked to the progression of human prostate cancer

Steroid hormones and their receptors are involved as initiators or promoters in prostate carcinogenesis. The intrauterine-perinatal period and maternal estrogen and testosterone levels have been proposed to be of etiologic importance in prostate tumorigenesis and cancer progression. The objective of this study was to analyze genetic polymorphisms in the androgen receptor ARStuI by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and in the estrogen receptor ER325 by PCR-single-strand conformational polymorphism (PCR-SSCP). In our study of 170 prostate cancer patients, ARStuI and ER325 genotypes and their association with disease progression and metastasis were analyzed. Age-adjusted logistic regression analysis indicates the association of ARStuI S1 allele with high-grade tumor (P = 0.033; OR = 3.0, 95% CI = 1.1-8.3) and the association of ER325 with high-grade tumor (P = 0.003; OR = 3.0, 95% CI = 1.4-6.4), advanced disease (P = 0.020; OR = 2.4, 95% CI = 1.1-5.1), risk of progression (P = 0.027; OR = 2.5, 95% CI = 1.1-5.7) and the presence of metastatic disease (P = 0.006; OR = 3.1, 95% CI = 1.4-6.8). In summary, this study has demonstrated androgen receptor (ARStuI) and estrogen receptor (ER325) genetic polymorphisms in prostate cancer patients and its association with disease progression and metastasis. Our results support the hypothesis that genetic factors related to steroid hormone receptors may influence the behavior of human prostate cancer.     

APOBEC3B deletion impacts on susceptibility to acquire HIV‐1 and its advancement among individuals in western India

APOBEC3B deletion polymorphism has been associated with risk of HIV‐1 acquisition and its progression. Therefore, we aimed to investigate the association of APOBEC3B ins/del polymorphism with risk of acquisition of HIV‐1 and its progression. In the present case–control study, we enrolled a total of 150 HIV‐infected individuals and 150 healthy controls. Polymorphism for APOBEC3B gene was genotyped by PCR. APOBEC3B ID, DD genotypes, and D allele were associated with higher risk of acquisition of HIV‐1 (p = 0.004, OR = 4.96; p = 0.03, OR = 3.55; and p = 0.004; OR = 1.60). The individuals with ID genotypes and combined genotype ID+DD of APOBEC3B in the presence of tobacco and alcohol showed the higher risk of advancement of HIV disease; however, risk could not reach statistical significance (OR = 1.14, 95% CI: 0.59–2.18; OR = 1.33, 95% CI: 0.83–2.15 and OR = 1.44, 95% CI: 0.77–2.69; OR = 1.50, 95% CI: 0.94–2.40). Individuals in advanced HIV disease stage and ID genotype and combined genotype ID + DD of APOBEC3B were more likely to be associated with advanced HIV disease stage but risk could not reach significant (OR = 1.50, 95% CI: 0.94–2.40; OR = 1.27, 95% CI: 0.88–1.84). Individuals with ID and DD genotype of APOBEC3B had influence on susceptibility to acquisition of HIV‐1. This suggests that APOBEC3B deletion may attenuate innate cellular immunity against HIV‐1 and thus confer the host persistence for HIV infection.     

载脂蛋白A5基因-1131T〉C多态性与冠心病易感性的关联研究

目的探讨载脂蛋白A5(apoA5)-1131T>C单核苷酸多态性与冠心病(CAD)发病风险之间的关系.方法经冠状动脉造影确诊的江苏地区冠心病患者235例,同一地区正常对照262名,采用PCR-RFLP分析对 apoA5基因的-1131T>C多态进行检测,比较不同基因型与个体血脂水平和冠心病患病风险的关系.结果 -1131T>C单核苷酸多态位点等位基因T、C频率在CAD组和正常对照组中分别为59.57%、40.43%和65.65%、34.35%.CAD组中C等位基因的频率高于对照组(P<0.05).与-1131TT基因型者比较,CC基因型者的冠心病患病风险显著增加(OR＝1.872,95%CI＝1.039-3.376,P=0.037),用Logistic回归模型对个体的年龄、性别、体重指数和抽烟、高血压等因素后,其患病风险仍明显增加(OR＝2.285, 95%CI＝1.222-4.274).对照组中不同基因型个体血浆甘油三酯水平差异有统计学意义(P=0.007),携带C等位基因的个体TG水平显著高于TT基因型个体.结论 apoA5基因-1131T>C多态性C等位基因是中国人群中冠心病发病的危险因素之一,且与血浆TG水平的变化密切相关.     

MMP9基因单核苷酸多态性与鼻咽癌遗传易感性的关系

目的研究MMP9基因单核苷酸多态性与广东人鼻咽癌患病风险及临床病理分期的关系。方法以聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析方法检测433例鼻咽癌患者和437例健康对照MMP9基因C-1562T和第6外显子R279Q基因型。结果吸烟显著增加鼻咽癌的患病风险（OR=4．01,95％CI=2．86—5．63）。MMP9基因C．1562T和R279Q基因型频率病例组与对照组相似,均未能增加鼻咽癌的发病风险,-1562CT／TF基因型相对于cc基因型AdOR=0．99,95％CI=0．70—1．39;279RQ／QQ基因型相对于RR基因型OR=0．96,95％C1=0．70～1．32;而且与吸烟增加鼻咽癌发病风险无交互作用。鼻咽癌病例组中,-1562CT／TT和RQ／QQ基因型并未表现出更高的T分期（经年龄、性别和吸烟校正后的OR值分别为1．23和0．84,P〉0．05）和淋巴结转移潜能（经年龄、性别和吸烟校正后的OR值分别为0．88和0．68,P〉0．05）。结论MMP9基因C-1562T和第6外显子R279Q多态性与广东地区鼻咽癌患病风险无关,可能不是广东人鼻咽癌发病遗传易感因素。     

CASP3和 CASP9基因多态性与胃癌遗传易感性的关联研究

目的 探讨凋亡相关基因caspase 3 (CASP3)、caspase 9 (CASP9)单核苷酸多态性与胃癌遗传易感性的关系.方法 采用以自然人群为基础的病例对照研究设计,对278例胃癌患者和以同年龄(± 5岁)、同性别、同居住地匹配为原则获得的278名对照进行研究.CASP3 rs12108497和 CASP9 rs4646018多态位点的基因分型采用聚合酶链反应-限制性片段长度多态性的方法分析.非条件Logistic回归分析计算基因多态与胃癌风险的相关性.结果 携带 CASP3 rs12108497 TC、CC基因型者患胃癌的风险较TT基因型者分别增加45%(OR=1.45,95%CI:1.01～2.07)和117% (OR=2.17,95%CI:1.15～4.08).未发现 CASP9 rs4646018基因多态与胃癌发病风险间存在显著关联.多基因模型显示携带1个或2个风险基因型的个体胃癌易感性增高(OR=1.60,95%CI:1.12～2.30).分层分析表明,携带1个或2个风险基因型的个体罹患胃癌的危险度在男性个体(OR=1.62,95%CI:1.05～2.49)、吸烟者(OR=1.87,95%CI:1.12～3.12)、饮酒者(OR=1.92,95%CI:1.02～3.65)和无肿瘤家族史者(OR=1.78,95%CI:1.18～2.68)中尤为明显.结论 CASP3 rs12108497 多态性会增加胃癌的发病风险.CASP9 rs4646018多态性与胃癌发病风险无关.

Abstract：

Objective To investigate the association between the apoptosis genes CASP3 (rs12108497) and CASP9 (rs4646018) polymorphisms and the risk of developing stomach cancer. Methods In this population-based case-control study, 278 cases with stomach cancer and 278 age (±5 years), gender, and residential area matched controls were recruited. The genotypes were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The unconditional Logistic regression analysis was utilized to calculate the odds ratios (OR) and 95% confidence intervals (CI). Results The individuals with TC, CC genotypes of rs12108497 locus had significantly increased risk of stomach cancer in comparison to those carrying TT genotype (OR=1.45, 95% CI: 1.01-2.07 for TC; OR=2.17, 95%CI: 1.15-4.08 for CC). However, the rs4646018 locus of CASP9 gene polymorphism was not related to stomach cancer risk. Compared with the subjects carrying the both low-risk genotypes, those carrying 1 or 2 high-risk genotypes had a noteworthy increased risk of stomach cancer (OR=1.60, 95% CI: 1.12-2.30). The combined high-risk genotypes appeared to be more evident in subjects of male (OR=1.62, 95% CI: 1.05-2.49), ever-smokers (OR=1.87, 95%CI: 1.12-3.12), ever-drinkers (OR=1.92, 95%CI:1.02-3.65) and no family history of cancer (OR=1.78, 95%CI: 1.18-2.68). Conclusion The current findings suggest that the polymorphism of CASP3 rs12108497 might be associated with the risk of stomach cancer. However, the CASP9 rs4646018 polymorphism may not be related to the stomach cancer risk.     

Association of a TRAF1 and a STAT4 gene polymorphism with increased risk for rheumatoid arthritis in a genetically homogeneous population

Rheumatoid arthritis (RA) is a multifactorial disease that is increasing in incidence worldwide. It is associated with a complex mode of inheritance, with many genes being involved in the development and progression of the disease. Genome-wide association studies in different populations have recently revealed a significant association between a TRAF1/C5 and a STAT4 polymorphism and the development of RA. In the present study we performed a case-control study in the population of the island of Crete, Greece, aiming to replicate the former findings in a genetically homogeneous cohort of patients. We found that mutated allele A or genotypes A/A and G/A of the TRAF1/C5 rs10818488 SNP were more common in individuals with RA than in control individuals (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.35-2.15, and OR = 2.22, 95% CI = 1.61-3.05, respectively). Similarly, mutated allele T or genotypes T/T and G/T of the STAT4 rs7574865 SNP were also associated with susceptibility to RA (OR = 1.9, 95% CI = 1.46-2.50, and OR = 2.37, 95% CI 1.73-2.25, respectively). Thus, we conclude that mutant alleles or genotypes of both polymorphisms examined are associated with the development of RA in our population.     

TIM3 gene polymorphisms in patients with chronic hepatitis B virus infection: impact on disease susceptibility and hepatocellular carcinoma traits

Hepatitis B virus (HBV) infection is associated with the development of acute and chronic liver diseases including hepatocellular carcinoma (HCC). T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3), which negatively regulates T-cell response and mediates phagocytosis of apoptotic cells, has been implicated in HBV infection and cancers. This study explored the polymorphisms of TIM3 gene in 535 patients with HBV-related liver diseases including 213 chronic hepatitis, 178 cirrhosis and 144 HCC, 72 HBV infection resolvers and 182 healthy controls and analyzed the effects of these polymorphisms on the disease susceptibility and HCC traits. TIM3-1541C/T, -1516G/T, -882C/T, -574G/T and +4259T/G polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Of the five polymorphisms genotyped, the allele T-containing genotypes (GT + TT), allele T and allele T-containing haplotype (CTCGT) of -1516G/T polymorphism were more frequent in HBV patients than in controls [P = 0.005, odds ratio (OR) = 2.300, 95% confidence interval (CI): 1.294-4.088; P = 0.004, OR = 2.266, 95% CI: 1.297-3.962; and P = 0.005, OR = 2.203, 95% CI: 1.260-3.854, respectively]. The allele T-containing genotypes and allele T of -1516G/T were associated with HCC tumor grade (P = 0.023 and P = 0.017, respectively) and lymph node metastasis (P = 0.024 and P = 0.017, respectively). These findings suggest that -1516G/T polymorphism in the promoter region of TIM3 gene may affect the disease susceptibility and HCC traits associated with HBV infection, potentially supporting the role of Tim-3 in T-cell dysfunction and exhaustion involved in persistent HBV infection and HCC development.     

Association of PTPN22 C1858T polymorphism and type 1 diabetes: a meta-analysis

Recently, protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism has been identified as a susceptibile gene for type 1 diabetes (T1D), but studies are inconsistence, In order to assess the association between PTPN22C1858T polymorphism and T1D based on different ethnicities, a meta-analysis was performed, including 26 studies, total of 16,240 patients and 17,997 controls. Meta-analysis was performed on T versus C, T/T+T/C versus C/C (dominant model) and T/T versus T/C+C/C (recessive model) in a fixed/random effects model. The results indicated an association between the PTPN22 C1858T polymorphism and T1D in all subjects. The overall odds ratio (OR) of T versus C using the fixed effects model was 1.948 (95% CI = 1.859～2.041, P < 0.001). After stratification by ethnicity, analysis revealed that the PTPN22 C1858T polymorphism T allele was significantly associated with T1D in Europeans, Americans (OR = 1.946, 95% CI = 1.852~2.045, P < 0.001; OR = 1.946, 95% CI = 1.690~2.242, P < 0.001, respectively). Meta-analysis of the T/T+T/C genotype and the T/T genotypes showed the same results as that shown by the PTPN22 C1858T polymorphism T allele. This meta-analysis suggests a possible association between the PTPN22 C1858T polymorphism and T1D, especially in European and American populations.