Maternal and offspring MTHFR gene C677T polymorphism as predictors of congenital atrial septal defect and patent ductus arteriosus

To observe the association of MTHFR gene C677T locus polymorphism with occurrence of congenital heart defects (CHDs), 21 patients with atrial septal defect (ASD), 35 patients with patent ductus arteriosus (PDA), one patient with both conditions combined, and their biological parents were collected as the case group. Another 104 normal individuals and their biological parents without a family history of birth defects were selected as the control group. MTHFR C677T genotypes of each sample were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed for the occurrence of ASD, the odds ratio (OR) of TT genotype was 4.08 [95% confidence interval (95% CI) = 1.28-13.24] compared with CT genotype. For the occurrence of PDA, the ORs of TT were 3.44 (95% CI = 0.89-16.13) and 2.38 (95% CI = 0.92-6.14) compared with CC and CT genotypes, respectively. Author as meant? Compared with CC + CT genotype combination, the ORs of TT were 3.95 (95% CI = 1.38-11.44) and 2.60 (95% CI = 1.02-6.36) for ASD and PSD respectively. The results also had sex differences and the statistical significance was only observed in male ASD and female PDA. The ORs of T allele carriers were 2.29 (95% CI = 1.08-4.92) and 1.88 (95% CI = 1.02-3.47) compared with C allele for the occurrences of ASD and PDA respectively. The analysis of parents genotype showed that the OR of TT mothers was 2.31 (95% CI = 0.96-5.59, P < 0.05) compared with (CC + CT) for the occurrence of PDA in offspring. So this study could give a clue that MTHFR C677T locus variation was related with occurrence of ASD and PDA, and the carriers of TT genotype and T allele had higher risk of diseases. The mother carrying TT genotype was associated with occurrence of PDA in offspring.     

Genetic variability of genes in NER pathway influences the treatment outcome of gastric cancer

We performed a study to investigate the role of ERCC1, ERCC2, ERCC5, XPA and XPC polymorphisms from perspective of the whole NER pathway in the prognosis of gastric cancer. A total of 410 gastric cancer patients were recruited between January 2010 and December 2011. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to analyze genotypes of ERCC1 rs11615 and rs3212986, ERCC2 rs13181 and s1799793, ERCC5 rs17655, XPA rs1800975 and XPC rs2228001. Our study found that carriers of ERCC1 rs3212986 TT genotype showed significantly favorable survival than wide-type GG genotype in multivariate analysis (OR=6.38, 95% CI=2.54-19.03), and patients with variant CC genotype of ERCC2 rs13181 exhibited better response to chemotherapy than those with AA genotype (OR=2.21, 95% CI=1.17-4.25). By Cox proportional hazards model, patients with variant TT genotype of ERCC1 rs3212986 exhibited longer PFS and OS than those who had GG genotype (for PFS, HR=0.37, 95% CI=0.17-0.75; for OS, HR=0.36, 95% CI=0.13-0.87). For ERCC2 rs13181 polymorphism, carriers with CC genotype demonstrated significantly increased hazards of progression of disease and death in multivariate model (for PFS, HR=0.48, 95% CI=0.26-0.88; for OS, HR=0.44, 95% CI=0.20-0.91). In conclusion, our finding suggests that ERCC1 rs3212986 and ERCC2 rs13181 gene polymorphism could influence the response to chemotherapy and clinical outcome of gastric cancer.     

The NAD(P)H:quinone oxidoreductase I C609T polymorphism modifies the risk of Barrett esophagus and esophageal adenocarcinoma.

PURPOSE: The role of genetic susceptibility to esophageal adenocarcinoma and its precursor lesion Barrett esophagus has not been fully elucidated. This study investigated the effect of polymorphisms in the manganese superoxide dismutase (MnSOD) and NAD(P)H:quinone oxidoreductase 1 (NQO1) genes in modulating the risk of developing Barrett esophagus or esophageal adenocarcinoma. METHODS: A total of 584 patients (146 esophagitis, 200 Barrett esophagus, 144 esophageal adenocarcinoma, and 94 controls) were genotyped for the MnSOD C14T and NQO1 C609T polymorphisms using polymerase chain reaction and restriction fragment length polymorphism analysis. RESULTS: The NQO1 TT genotype was less common in Barrett esophagus (2.0%) and esophageal adenocarcinoma (1.4%) patients, compared with both esophagitis patients (7.6%) and controls (5.4%). After adjustment for sex, age, body mass index, reflux symptoms, and smoking status, patients with the homozygous TT genotype had a 4.5-fold decreased risk of developing Barrett esophagus (odds ratio = 0.22, 95% confidence interval = 0.07-0.76, P = 0.01) and a 6.2-fold decreased risk of esophageal adenocarcinoma (odds ratio = 0.16, 95% confidence intervals = 0.03-0.94, P = 0.04) compared with individuals with the TC and CC genotypes. No significant differences between groups were observed for the MnSOD polymorphism (P = 0.289). CONCLUSIONS: Overall, the results of this study suggest that the NQO1 TT genotype may offer protection from reflux complications such as Barrett esophagus and esophageal adenocarcinoma.     

Association between the interaction of SMAD3 polymorphisms with body mass index and osteoarthritis susceptibility

Purpose: This study aimed to investigate the relationship between the interaction of SMAD3 polymorphisms (rs12102171 and rs2289263) with body mass index (BMI) and osteoarthritis (OA) susceptibility. Methods: This study involved 112 OA patients and 120 healthy people. The controls were frequency-matched with the cases by age and sex. Hardy-Weinberg equilibrium (HWE) was tested by χ² test in the control group. The rs12102171 and rs2289263 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The relative risk of OA was represented by odds ratio (OR) with 95% confidence interval (CI) calculated by chi-squared test. Gene-environment interaction was analyzed by crossover analysis. Results: The TT genotype and T allele of SMAD3 rs12102171 polymorphism were more frequent in case than control groups (P=0.04 in both of two polymorphisms), which increased the risk of OA (OR=3.39, 95% CI=1.03-11.11 and OR=1.64, 95% CI=1.03-2.59). GG genotype and G allele were also the risk factors for OA (OR=3.22, 95% CI=1.09-9.51 and OR=1.57, 95% CI=1.02-2.42). The BMI had interactions with genotype CC and CT+TT of rs12102171 and TT and TG+GG of rs2289263 (rs12102171: OR=2.15, P=0.02 and OR=3.99, P=1.00×10^-3; rs2289263: OR=2.73, P=4.00×10^-3 and OR=4.67, P=0). Conclusions: CC and CT+TT and TT and TG+GG genotypes of SMAD3 rs12102171 and rs2289263 polymorphisms together with BMI may be susceptible factors to OA, and interactions there between can possibly confer risk to OA.     

Association of the platelet glycoprotein Ia C807T/G873A gene polymorphism and thrombosis in Behçet patients

Thrombosis is a common complication of Beh?et disease and the pathogenic mechanism of thrombotic tendency in Beh?et disease is not well known. Several platelet membrane glycoprotein gene polymorphisms have been identified as risk factors for thrombosis. This study aimed to evaluate the possible role of the GP Ia C807T/G873A polymorphism as a risk factor for thrombosis in Beh?et disease. We determined the prevalence of platelet glycoprotein Ia C807T/G873A gene polymorphism in Beh?et patients. Genomic DNA was obtained from 20 patients with Beh?et disease and 61 controls. All individuals were of Turkish ancestry and were genotyped for the GP Ia C807T/G873A polymorphism with real-time PCR method by LightCycler system. The 807 CC, CT and TT genotypes corresponded with 873 GG, GA and AA genotypes, respectively. Complete linkage between the 807 and 873 sites was found in all samples. The 807CC(873 GG), 807CT(873GA), 807TT(873AA) genotypes found to be 45.9%, 45.9% and 8.1% in controls and 30.0%, 55.0% and 15.0% in patients with Beh?et disease, respectively. The Odds Ratio for BD (OR = 1.97; 95% confidence interval (CI): 0.42-9.13) is high for the 807 TT genotype compared with controls. Thrombosis was found in 7 cases of Beh?et disease group: five cases have 807CT, one case has 807TT genotype and one case has 807CC genotype. Our data indicate hat patients with BD are affected by the glycoprotein Ia gene 807TT genotypes and carrying 807T allele. The risk of thrombosis is significantly higher in patients who have 807TT and 807CT genotypes than in patients who have 807CC genotype.     

The Influences of CD14 −260C>T Polymorphism on Survival in ICU Critically Ill Patients

In order to analyze the effect of the two different versions of the cluster of differentiation 14 (CD14) receptor recognizing gene on survival, we determined the ?260C>T single nucleotide polymorphism (SNP) frequencies in 514 critically ill patients. We compared the ?260TT homozygotes with ?260C allele carriers (?260CC and ?260CT genotypes) and we demonstrated—260TT patients had the highest survival rate (82% vs 64%; p < 0.001; OR = 2.52, 95% CI = 1.43–4.46). We performed binary logistic regression, incorporating both ?260C>T genotype groups and the main clinical predictors to exclude other risk factors that could influence the outcome from critical illness: higher age, APACHE II score, and length of stay at hospital, and the occurrence of sepsis and septic shock were risk factors to Intensive Care Unit (ICU) patient's mortality, but the ?260TT genotype was protective factor toward survival (p = 0.001; OR = 3.08 95%CI = 1.54–5.98). Among septic and septic shock patients, ?260TT genotype was also protective factor toward survival (p = 0.001; OR = 3.11 95%CI = 1.63–6.66 to septic patients, and p = 0.001; OR = 3.80 95%CI = 1.68–8.58 to patients with septic shock). Our results and our hypothesis suggest that the higher ?260TT genotype frequency in ICU survivor patients is possibly explained by a beneficial effect on innate immunity signaling.     

Influence of the cystathionine beta-synthase 844ins68 and methylenetetrahydrofolate reductase 677C>T polymorphisms on folate and homocysteine concentrations

A high homocysteine, low folate phenotype is a feature of many diseases. The effect of the cystathionine beta-synthase (CBS) 844ins68 polymorphism on homocysteine and folate concentrations was examined alone and in the context of the 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C>T polymorphism in a Northwestern European male population. The MTHFR 677TT genotype is known to be associated with increased homocysteine and decreased folate relative to CT heterozygotes and CC homozygotes in this and other populations. MTHFR 677TT homozygotes who were also CBS 844ins68 carriers had homocysteine and folate concentrations similar to those of individuals with the MTHFR 677CT and CC genotypes. Homocysteine levels in MTHFR 677TT subjects carrying the CBS 844ins68 allele were 24.1% lower than in non-carriers (6.66 vs 8.77 micromol/l, P=0.045), and serum folate levels were 27.7% higher (11.16 vs 8.74 nmol/l, P=0.034). These findings suggest that the CBS 844ins68 allele 'normalizes' homocysteine and folate levels in MTHFR 677TT individuals.     

The association between interleukin-1β gene polymorphisms and the risk of breast cancer: a systematic review and meta-analysis

IntroductionIt is reported that there is a close association between interleukin-1β (IL-1β) gene polymorphisms and breast cancer risk. However, the results remain controversial.Material and methodsEligible published articles were searched in PubMed, Embase, and Web of Science databases up to June 2018. Odds ratios with 95% confidence intervals were used to identify potential links between IL-1β genetic polymorphisms and the risk of breast cancer.ResultsFrom our results, we found that three common polymorphisms in IL-1β (rs16944, rs1143634, rs1143627) had no significant associations with breast cancer risk in all genetic models. Based on the analysis from ethnic subgroups, there was a higher risk of breast cancer for rs16944 polymorphism in the recessive model and heterozygous model among Asians (TT vs. CC+CT: 1.229, 95% CI: 1.063–1.422, p = 0.005; TT vs. CT: 1.211, 95% CI: 1.057–1.388, p = 0.006). For the rs1143627 polymorphism, a significantly decreased breast cancer risk was observed in the dominant model only in Asians (CT+TT vs. CC: OR = 0.944, 95% CI: 0.897–0.994, p = 0.027). After stratifying patients according to the menopausal state, we found that polymorphism of rs1143627 correlated with reduced breast cancer risk among post-menopausal women in three genotype models: allele, recessive model and homozygous model (T vs C: 0.859, 95% CI: 0.753–0.98, p = 0.024; TT vs. CC+CT: 0.727, 95% CI: 0.576–0.918, p = 0.007; TT vs. CC: 0.743, 95% CI: 0.626–0.882, p = 0.001). As for other analyses with reference to source of controls and genotyping methods, no significant association between IL-1β polymorphism and breast cancer risk was demonstrated.ConclusionsThe rs16944 and rs1143627 polymorphisms are significantly associated with the risk of breast cancer only in Asian people and in post-menopausal women respectively.     

Effect of IL-1β and TNF-α polymorphisms on the prognosis and survival of gastric cancer patients

So far, a number of association studies have focused on the effect of polymorphisms in IL-1β and TNF-α genes on the susceptibility to gastric cancer (GC). Here, we evaluate the possible association between common polymorphisms in the IL-1β and TNF-α genes with various clinicopathological characteristics, including overall survival of GC patients. Restriction fragment length polymorphism analysis was performed for IL-1β-31(T?>?C) and IL-1β-511(C?>?T) and TNF-α-857 (C?>?T) polymorphisms in 130 GC patients. IL-1β-31CC and IL-1β-511TT genotypes held a significantly lower risk of lymphatic invasion (IL-1β-31CC vs. others: adjusted OR?=?0.39, 95% CI?=?0.15-0.96, P?=?0.04, IL-1β-511TT vs. others: adjusted OR?=?0.23, 95% CI?=?0.08-0.67, P?=?0.007). The IL-1β-31CC and IL-1β-511TT genotypes were weakly associated with reduced risk of venous invasion (IL-1β-31CC vs. others: adjusted OR?=?0.35, 95% CI?=?0.12-1.05, P?=?0.06, IL-1β-511TT vs. others: adjusted OR?=?0.32, 95% CI?=?0.08-1.20, P?=?0.09). The IL-1β-511TT genotype was also weakly associated with reduced risk of lymph node metastasis (IL-1β-511TT vs. others: adjusted OR?=?0.42, 95% CI?=?0.17-1.04, P?=?0.06). When the TNF-α-857CT and TNF-α-857-TT genotypes were considered as T carrier, the patients with TNF-α-857T carrier showed significantly better overall survival than patients with CC genotype (P?=?0.011). GC patients who have both IL-1β-31 CC and IL-1β-511 TT genotypes and have at least one of protective genotypes (IL-1β-31 CC, IL-1β-511 TT, TNF-α-857 T carrier) were also associated with better prognostic factors, such as lymphatic and venous invasion better survival. IL-1β-31CC, IL-1β-511TT genotype, and TNF-α-857T carrier may have protective effect against GC progression.     

Genetic polymorphisms in nucleotide excision repair pathway influences response to chemotherapy and overall survival in osteosarcoma

We analyzed the role of genetic polymorphisms of six important NER pathway genes in response to chemotherapy and clinical outcome of osteosarcoma patients. A prospective study including 172 osteosarcoma patients was conducted between January 2009 and January 2011. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs1799793, ERCC4 rs1800067, ERCC5 rs1047768, XPA 1800975, and XPC rs2228000 and rs2228001 gene polymorphisms. By logistic regression analysis, TT genotype of ERCC1 rs11615 genetic polymorphism was significant correlated with poor response to chemotherapy when compared with wide-type genotype (OR=0.27, 95% CI=0.10-0.71). AC and CC genotype of ERCC1 rs2298881 were significantly associated with poor response to chemotherapy when compared with AA genotype (For AC genotype, OR=0.45, 95% CI=0.21-0.97; for CC genotype, OR=0.19, 95% CI=0.06-0.58). By Cox proportional hazards regression analysis, TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 suffered a 3.16 and 3.57-fold increased hazards of death (For ERCC1 rs11615, HR=3.16, 95% CI=1.19-9.16; for ERCC1 rs2298881, HR=3.57, 95% CI=1.10-11.35). In conclusion, our findings suggest that ERCC1 rs11615 and ERCC1 rs2298881 genetic polymorphisms are significantly associated with poor response to chemotherapy and unfavourable survival of osteosarcoma.     

Genetic association between low-density lipoprotein receptor-related protein gene polymorphisms and Alzheimer's disease in Chinese Han population

Alzheimer's disease (AD) is the most common neurodegenerative disorders in the elderly. Low-density lipoprotein receptor-related protein (LRP), as a receptor of apolipoprotein E (APOE), APP, and alpha2 macroglobulin (alpha2-M), keeps the balance between degeneration and production of beta-amyloid protein (Abeta) clearance. Its gene had been defined as a candidate gene for AD, but the results were not universal. Total 496 AD patients and 478 controls were recruited in Chinese Han population and real-time PCR was used to detect the polymorphism of LRP C766T. Multiple logistic regression, Chi-square test and survival analysis were performed to explore the association. The distribution of LRP genotypes and alleles was significantly different between cases and controls, and T allele could reduce the risk for developing AD (OR of CT genotype: 0.57; 95% CI: 0.38-0.85, rho=0.003; OR of T allele: 0.57; 95% CI: 0.39-0.83, rho=0.003). TT genotype carriers had 5 years later for developing AD compared with CC genotype carriers, but survival analysis did not conform this (LRP TT vs. CT and CC log rank chi(2)=2.71, rho=0.26). The distribution of LRP C766T genotypes and alleles was different among different severity stratified by MMSE yet (rho=0.26). Our data suggested that the polymorphism of LRP C766T was strongly associated with AD and T allele might be a protective factor for AD in Chinese Han population.     

ATM基因rs227060位点单核苷酸多态性与肺癌易感性的相关性

目的:探讨共济失调毛细血管扩张症突变基因(ataxia telangiectasia mutated,ATM)rs227060位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)与肺癌易感性之间的相关性.方法:采用聚合酶链反应-SNP敏感性分子开关方法,检测225例肺癌患者和128例健康体检者ATM基因rs227060多态位点等位基因以及基因型频率分布特点;并应用非条件Logistic回归法统计分析rs227060单核苷酸多态性与肺癌的相关性.结果:rs227060多态位点共检测出CC,CT,TT三种基因型和C,T两种等位基因,其在肺癌组与对照组的基因型分布频率为:CC基因型17.3％与29.7％、CT基因型61,4％与59.3％、TT基因型21.3％与11％,两组间基因型频率和等位基因频率分布差异均有统计学意义(P＜0.05).在对ATM rs227060基因型的多态性分析过程中发现:吸烟史在肺癌组与对照组相比差异无统计学意义(P＞0.05),而年龄、性别、肿瘤家族史在肺癌组与对照组相比差异均有统计学意义(P＜0.05);且以CC基因型作为对照,携带TT基因型的个体患肺癌的风险是携带CT基因型个体的3.49倍(OR=1.829;95％CI:1.045～3.199).结论:ATM基因rs227060位点单核苷酸多态性与肺癌易感性存在相关性,且携带TT基因型可增加肺癌的发病风险.     

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.     

广东汉族女性TRIM31基因单核苷酸多态性与乳腺癌易感性的相关性研究

目的:探讨TRIM31(Tripartite motif containing 31)基因rs1116221位点单核苷酸多态性(Single nucleotide poly-morphisms,SNP)与广东汉族女性乳腺癌易感性的关系。方法:利用MassARRAY-IPLEX SNP分型技术,对南方医科大学南方医院的216例广东汉族乳腺癌患者及216例同期健康体检者TRIM31基因的多态性位点rs1116221进行基因分型,采用χ2检验方法统计分析病例组与对照组的基因型分布频率的差异,采用非条件Logistic回归计算比数比(Odds ratio,OR)和95%可信区间(Confidence interval,CI)对该位点多态性与乳腺癌易感性的相关性进行评价。在此基础上,在病例组中根据临床雌激素受体(Estrogen receptor,ER)和孕激素受体(Progesterone receptor,PR)的免疫组化结果进一步分层分析。结果:TRIM31基因位点rs1116221在广东汉族女性中存在CC、CT、TT 3种多态性,病例-对照分析显示,该位点基因型分布频率在两组中无统计学差异(P>0.05);进一步分层分析发现,该位点的基因型分布在ER阳性/阴性(+/-)分组中存在差异,且具有统计学意义(P=0.034),携带杂合基因型CT的个体更倾向于ER(+)乳腺癌(OR=2.67,95%CI:1.02～7.02);而在PR阳性/阴性(+/-)分组中无统计学差异。结论:基因TRIM31的rs1116221位点多态性与乳腺癌患病风险之间无明显相关性,但该位点的杂合基因型与乳腺癌ER阳性(+)明显相关。     

微小RNA-181基因家族单核苷酸多态性和基因表达水平与缺血性脑卒中遗传易感性的关系

目的 探讨微小RNA（miR）-181基因家族rs16927589、rs77418916和rs8108402位点单核苷酸多态性（SNP）与缺血性脑卒中(IS)遗传易感性之间的关系;比较对照组与IS组中miR-181基因家族表达水平的差异,进一步探讨与基因表达水平之间的关系,为IS的防治工作提供帮助。 方法 使用SNaPshot技术对349例IS患者和372例对照组进行SNP基因分型检测,并用DNA测序法加以验证;使用日立7600生化仪检测对照组和IS组血脂水平;用ABI7500 Real-time PCR仪检测对照组和IS组外周血单核细胞miR-181基因家族的表达水平。 结果 关于rs8108402位点有CC、CT、TT 3种基因型,对照组和IS组基因型及等位基因频率对比发现,与CC基因型比较,CT基因型的携带人群患IS的风险性明显增高,TT基因型携带者患IS风险降低［CC vs CT:优势比（OR）=1.56,95%置信区间（CI）,1.11~2.18, P<0.05; CC vs TT: OR=0.25,95%CI, 0.10~0.62, P<0.01］,等位基因分析未发现相关性;rs16927589位点检测出TT、CT、CC 3种基因型,rs77418916位点有AA、AT、TT 3种基因型,对照组与IS组对比,未发现相关性。对rs8108402位点分层分析表明,携带CC基因型的IS患者其低密度脂蛋白（LDL-C）比携带CT基因型的IS患者高（P<0.05）,rs8108402位点多态性可能与IS的临床表现有相关性。IS组中,外周血单核细胞中miR-181a、miR-181b和miR-181c的表达明显高于对照组,差异有统计学意义（P<0.05）,而miR-181d的表达低于对照组,差异无计学意义（P>0.05）;对阳性位点rs8108402位点多态性与基因表达水平进一步分析发现,rs8108402位点多态性与基因表达水平无相关性。 结论 MiR-181c基因rs8108402位点CT和TT基因型可增加IS患病风险,CTC单倍型可增加IS患病风险。MiR-181c基因rs8108402位点多态性与LDL-C的高低有相关性,携带CC基因型的IS患者,其LDL-C水平较携带CT基因型患者高。MiR-181基因家族在正常对照组和IS组中的表达有明显差异,miR-181基因家族可能是IS的潜在的预测靶标和治疗靶基因。     

载脂蛋白A5基因-12238T/C多态性与新疆维吾尔族冠心病的相关性

目的 研究载脂蛋白A5(apolipoprotein A5,APOA5)-12238T/C多态性与新疆维吾尔族冠状动脉粥样硬化性心脏病(简称冠心病)及血脂水平的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法,对344例冠心病患者和408例同期入院冠状动脉造影结果阴性的患者(对照组)APOA5基因-12238T/C多态性进行检测,同时进行血脂水平的测定.结果 APOA5基因-12238T/C的3种基因型在冠心病组的分布频率分别为:TT型50.00%,TC型43.31%,CC型6.69%;在对照组的分布分别为:TT型39.95%,TC型45.10%,CC型14.95%,两组基因型分布差异具有统计学意义(P＜0.01).通过Logistics回归校正了年龄、性别,吸烟史、血脂、高血压、糖尿病史等影响因素后,CC基因型的个体患冠心病的风险是TT型的0.328倍(OR=0.328,95%CI:0.154～0.700).冠心病组-12238T/C基因型亚组间的甘油三酯水平的差异有统计学意义(P＜0.05),CC及TC基因型较TT型有更低的甘油三酯水平.结论 APOA5基因-12238T/C多态性对新疆维吾尔族人血清甘油三酯水平有影响,并且与冠心病的发生有一定的相关性,CC基因型可能是冠心病发生的一个保护因素.

Abstract：

Objective To investigate the association of the -12238T/C polymorphism of apolipoprotein A5 (APOA5) gene with coronary heart disease (CHD) and the influence of serum lipid levels in Chinese Uygur population of Xinjiang. Methods The -12238T/C polymorphism of APOA5 gene in 344 patients with CHD and 408 controls was analyzed by polymerase chain reaction restriction fragment length polymorphism; the serum lipid levels were detected as well. Results The frequencies of CC, TC and TT genotype were 6.69%, 43.31% and 50. 00% in the CHD group, while they were 14. 95%, 45.10% and 39.95% in the control group. There was significant difference in the distribution of genotypes between the two groups (P＜ 0. 01). Logistic regression analyses adjusted for age, gender, smoking, serum total cholesterol, presence of hypertension and diabetes revealed that individuals carrying CC genotype had an increased risk of CHD compared with TT genotype (OR=0. 328,95% CI: 0. 154-0. 700). There was also significant difference in serum triglyceride level in genotypes between these two groups (P＜0.01). Patients in CHD group who carried CC and TC genotypes had lower serum triglyceride level than the TT genotype carriers. Conclusion The - 12238T/C polymorphism of APOA5 gene has influence on the serum triglyceride level in Uygur population of Xinjiang. This polymorphism might be associated with development of CHD, and the CC genotype might be a protective factor in the development of CHD.     

ABCB1 Allele Polymorphism Is Associated with Virological Efficacy in Naïve HIV-Infected Patients on HAART Containing Nonboosted PIs But Not Boosted PIs

Abstract

Objective: To assess the effect of the multidrug resistance-1 single nucleotide polymorphism (ABCB1 SNP) C3435T in exon 26 on the virological responses to first-line protease inhibitor (PI)-containing HAART regimens. Method: A cohort of 182 HIV-infected patients with a PI-containing HAART regimen initiated from 1997 to 2004 was enrolled. Time to the first indetectable viral load (VL) was determined in patients with the CC, CT, or TT genotype. Results: There were 37%, 44%, and 19% of patients who had the CC, CT and TT genotypes, respectively. The median estimated times to VL indetectability in the CC, CT, and TT groups were respectively 5.9, 3.9, and 4.8 months (p = .06). In patients on a non-boosted PI regimen, ABCB1 genotype was associated with time to VL indetectability that was shorter in patients with the CT than CC genotype (CT vs. CC, hazard ratio [HR] = 0.62, p = .02; TT vs. CC, HR = 0.72, p = .21). This association was not found in patients with first-generation boosted PI-containing regimens and especially not with second-generation boosted PI-containing regimens. Conclusion: Our results show that the ABCB1 SNP in exon 26 is associated with virological efficacy in HIV-infected patients treated with non-boosted PI-containing regimens but not with those containing boosted PIs, particularly of the second generation.