Association analysis between polymorphisms in the conserved dopamine neurotrophic factor (CDNF) gene and cocaine dependence

Cocaine-induced neuroplasticity changes in the mesocorticolimbic dopamine systems are thought to be involved in the pathophysiology of cocaine dependence. Since neurotrophic factors have been observed to prevent/reverse and mimic cocaine-induced neurobiological changes in the brain, related genes are plausible candidates for susceptibility to cocaine dependence. The novel conserved dopamine neurotrophic factor protein (CDNF) promotes the survival, growth, and function of dopamine-specific neurons and is expressed in brain regions that undergo cocaine-induced neuroplasticity. In this study, we hypothesize that polymorphisms in the CDNF gene (CDNF/ARMETL1) contribute to increased risk for cocaine dependence. Cocaine dependent individuals (n = 351) and unaffected controls (n = 257) of African descent were genotyped for four single nucleotide polymorphisms (SNPs) in the CDNF gene (rs11259365, rs7094179, rs7900873, rs2278871). We observed no significant differences in allele, genotype, or haplotype frequencies between cases and controls for any of the tested SNPs. Our study suggests that there is no association between variants in the CDNF gene and cocaine dependence. However, additional studies using larger sample sizes, comprehensive SNP coverage, and clinically homogenous populations are necessary before confidently excluding CDNF as a significant genetic risk factor for cocaine dependence.     

IL-33基因单核苷酸多态性与中国南方汉人炎症性肠病临床表型相关*

 目的：探讨白细胞介素33（IL-33）基因单核苷酸多态性（SNP）与中国南方汉人炎症性肠病（IBD）的关系。方法：通过HapMap数据库筛选出IL-33基因8个SNP序列标签;对250例克罗恩病（CD）患者、115例溃疡性结肠炎（UC）患者及622名健康对照采用MALDI-TOF MS技术进行基因分型检测。结果：8个SNP位点的基因型及等位基因频率在病例（包括CD及UC）及对照组中无明显差异（P>0.05）。基因型-临床表型分析发现多个SNP位点与CD部分临床表型相关：rs10118795 T等位基因是肠外表现的保护因素（P<0.05, OR=0.513, 95% CI： 0.281～0.938）,而rs7025417 CC基因型是肠外表现的危险因素（P<0.05, OR=1.363, 95% CI： 1.006～1.846）;rs10118795 C等位基因降低肛周病变风险（P<0.05, OR=0.480, 95% CI： 0.232～0.994）,而rs10975519 CC基因型增加肛周病变风险（P<0.05, OR=2.054 , 95% CI： 1.053~4.009）;rs10975509 G等位基因是上消化道型CD的危险因素（P<0.05, OR=3.570, 95% CI： 1.328~9.600）,且其A等位基因携带者发生回结肠型CD的风险增加（P<0.05, OR=0.613, 95% CI： 0.377~0.996）;在治疗方面,rs10118795、rs10975509和rs7025417基因型均与CD患者英夫利昔单抗治疗后30周黏膜愈合相关（P<0.05,P<0.01,P<0.05）。UC患者中,未发现这8个SNP位点影响其临床表型（P>0.05）。结论：本研究中IL-33基因8个SNP位点不增加中国南方人群CD及UC发病风险,但部分位点影响CD的临床表型,某些SNP位点可能成为预测英夫利昔单抗疗效的标志物。     

Association between the three functional miR-146a single-nucleotide polymorphisms,rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164?G?>?C was found to be associated with increased risk of multiple sclerosis (CC?+?CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC?+?GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC?+?GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC?+?GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC?+?CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C?>?T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC?+?TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC?+?CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A?>?G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.     

Association of RIP2 gene polymorphisms and systemic lupus erythematosus in a Chinese population

The aim of this study was to investigate the association of receptor interacting protein 2 (RIP2) single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A case-control study was performed on the SNPs rs16900617 and rs16900627 in 590 Chinese SLE patients and 660 healthy controls. These SNPs were typed by TaqMan allele discrimination assays. We found a significant association of rs16900617 G allele [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.41-0.72] and rs16900627 G allele (OR = 1.28, 95% CI 1.04-1.58) with SLE. Significant differences in genotype frequency distribution were also found in SLE and control individuals (rs16900617: AG versus AA, OR = 0.59, 95% CI 0.44-0.81; GG versus AA, OR = 0.08, 95% CI 0.01-0.65; AG + GG versus AA, OR = 0.55, 95% CI 0.41-0.75; rs16900627: AG versus AA, OR = 1.51, 95% CI 1.17-1.93; AG + GG versus AA, OR = 1.43, 95% CI 1.13-1.82). Analysis of the haplotypes revealed that two haplotypes of AG and GA were also significantly associated with SLE (OR = 1.37, 95% CI 1.11-1.70; OR = 0.60, 95% CI 0.45-0.79). Our findings suggest that the RIP2 gene polymorphisms may be associated with susceptibility to SLE in the Chinese population.     

Association between PKA gene polymorphism and NTDs in high risk Chinese population in Shanxi

Objective: This study aimed to investigate the single nucleotide polymorphisms (SNPs) of PKA and neural tube defects (NTDs) in Chinese population. Method: A total of 183 NTDs cases and 200 healthy controls were used in this study. 7 selected single nucleotide polymorphism (SNP) sites in the PKA gene were analyzed with MassArray high-throughput DNA analyzer with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. A series of statistical methods were carried out to investigate the correlation between the SNPs and the patient susceptibility to NTDs. Results: Statistical analysis showed a significant correlation between the SNP sites rs12132032 in PRKACB and NTDs. The AA genotype, A-allele and dominant AA in rs12132032 significantly increased the incidence of NTDs especially anencephaly (OR=3.87, 95% CI: 1.80-8.34 with genotype; OR=2.08, 95% CI: 1.43-3.04 with allele; OR=3.10, 95% CI: 1.53-6.26 with dominant). The T-allele of rs594631 in PRKACB was correlative with NTDs in male but not in female. Conclusions: The gene polymorphism loci rs12132032 in PRKACB maybe a potential risk factor for anencephaly in Chinese population from Shanxi, while gender susceptibility may influence the correlation.     

A Single Nucleotide Polymorphism of IL-21 Gene is Associated with Systemic Lupus Erythematosus in a Chinese Population

The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in IL-21 gene with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A total of 605 independent SLE patients and 666 unrelated healthy controls were recruited for the case?Ccontrol association study. Two SNPs (rs2221903 and rs907715) within the IL-21 gene intronic region were genotyped by TaqMan SNP allelic discrimination methods. The allele T frequency of SNP rs2221903 in patients and healthy controls was 89.4?% and 86.8?%, respectively [T versus C, odds ratio (OR)?=?1.287, 95?% confidence interval (CI)?=?1.010?C1.640]. No significant differences in genotype frequencies were shown between SLE patients and healthy controls (P value?=?0.705, 0.406, respectively). However, the effect of recessive model (TT versus CC?+?CT, OR?=?1.368, 95?% CI?=?1.050?C1.781) was observed. Distributions of allele and genotype frequencies of the SNP rs907715 showed no significant differences between SLE patients and controls. Analysis of the haplotypes revealed that CC haplotype was significantly associated with SLE (OR?=?0.734, 95?% CI?=?0.573?C0.941). In conclusion, our findings suggest that a SNP (rs2221903) and CC haplotype (rs2221903 and rs907715) of the IL-21 gene is associated with SLE in the Chinese population. However, further studies are needed to determine the functional consequences of this polymorphism with SLE susceptibility.     

Asthma Endophenotypes and Polymorphisms in the Histamine Receptor HRH4 Gene

Background: Histamine as an inflammatory mediator plays an important role in chronic allergic and asthmatic conditions. However, the role of genetic polymorphisms of the histamine receptor HRH4 (histamine receptor H4) gene in asthma susceptibility and endophenotypes has not been studied yet. Our aim was to investigate the possible association between single nucleotide polymorphisms (SNPs) in the HRH4 gene and asthma or some endophenotypes of asthma. Methods: Twenty-one SNPs of the HRH4 gene were genotyped in 313 asthmatic patients and 360 controls using Sequenom? iPLEX? Gold Genotyping Technology. Results: Genotype distribution of three HRH4 SNPs, namely rs17187619 [p = 0.002; odds ratio, OR (95% confidence interval, CI) = 2.4 (4.1-1.4)], rs527790 [p = 0.0002; OR (95% CI) = 3.3 (6.1-1.8)] and rs487202 [p = 0.00007; OR (95% CI) = 3.5 (6.6-1.9)] differed significantly between patients with or without infection-induced asthma. Haplotypes, which included the rs4800573-rs527790 CC allele combination, were found to be associated with infection-induced asthma [p = 0.0009, OR (95% CI) = 0.5 (0.4-0.8)]. The rs487202-rs574913 CA haplotype was more frequent among patients with infection-induced asthma [p = 0.0006, OR (95% CI) = 1.9 (1.3-2.6)]. None of the SNPs contributed directly to the risk of asthma. Conclusions: Our results suggest that genetic variation in the HRH4 gene might influence the pathogenesis of infection-induced asthma.     

PITX3 polymorphism is not associated with Parkinson's disease in a Chinese population

Several studies have indicated that three PITX3 single nucleotide polymorphisms (SNPs), rs2281983, rs4919621 and rs3758549, are likely to be associated with Parkinson's disease (PD) in Caucasians. Some studies also suggested an age-of-onset effect. We recently reported that allele and genotype frequencies did not differ between late-onset PD (LOPD) patients and controls for all three SNPs. To extend the analysis to early-onset PD (EOPD) patients, and to test whether an age-of-onset effect exists in Chinese, we genotyped these SNPs in 290 Chinese EOPD patients using a ligase detection reaction (LDR). For all three SNPs, allele and genotype frequencies did not differ between total PD patients and controls, between LOPD patients and controls, between EOPD patients and controls, or between LOPD and EOPD patients. Our results suggest that these PITX3 SNPs do not contribute to the risk of developing PD in EOPD or LOPD in Chinese.     

Association between VEGF polymorphisms (936c/t, -460t/c and -634g/c) with haplotypes and coronary heart disease susceptibility

Aim: Our aim was to investigate the association between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor (VEGF) and coronary heart disease (CHD) susceptibility in Chinese Han population. Methods: 144 CHD patients and 150 healthy individuals were enrolled in the study. Three SNPs (936C/T, -460T/C and -634G/C) of VEGF were chose and then were genotyped with Sequenom time-of-flight mass spectrometry (TOFMS). Odds ratio (OR) with 95% confidence interval (CI) were used to evaluate the association of genotypes and haplotypes and CHD susceptibility. Results: The frequencies of -460T/C CC genotype (13.6%) was found higher in the case group than that of control group (6.7%), which indicated that CC genotype was a risk factor for CHD (OR=2.50, 95% CI=1.10-5.68). Correspondently, the C allele appeared to increase the risk of CHD (OR=1.54, 95% CI=1.07-2.22). For -634G/C polymorphism, the risk of the CC genotype carrier for CHD increased 2.24 fold compared to the wild genotype. Moreover, -634G/CC allele was significantly associated with CHD susceptibility (OR=1.65, 95% CI=1.15-2.36). In addition, +936C/T CT genotype and C allele appeared to be a genetic-susceptibility factors for CHD (OR=2.43, 95% CI=1.44-4.10; OR=1.95, 95% CI=1.26-3.02). The haplotype analysis showed that T-C-T, C-C-C and C-G-C haplotypes all could increase the risk for CHD (OR: 2.43, 2.77 and 2.33). Conclusion: we concluded VEGF polymorphisms were associated with CHD susceptibility. Moreover, the haplotypes of T-C-T, C-C-C and C-G-C all could increase the risk for CHD.     

Association between PARK16 and Parkinson's disease in the Han Chinese population: a meta-analysis

PARK16 was reported to alter the risk for Parkinson's disease (PD) in the Japanese population. However, its role in Han Chinese PD patients has not been well established. Herein, we investigated the effect of 4 single-nucleotide polymorphisms (SNPs) within the PARK16 locus, including rs823128, rs947211, rs823156, and rs11240572, on the risk of PD by genotyping 497 Taiwanese patients with PD and 500 age-matched control subjects. The results were then meta-analyzed with available genetic association studies in the same population. The meta-analysis showed that PD patients demonstrated a lower frequency of the rs823128 G allele (11.93%) than control subjects (14.04%; odds ratio [OR] 0.83, 95% confidence interval [CI] 0.72–0.96, p = 0.010). The frequency of the rs947211 A allele (40.35%) in PD patients was lower than in control subjects (43.01%; OR 0.90, 95% CI 0.80–0.99, p = 0.047). The rs823156 G allele was less frequently seen in PD patients (17.32%) than in control subjects (21.35%; OR 0.77, 95% CI 0.69–0.86, p < 0.001). A lower frequency of the rs11240572 A allele was found in PD patients (14.01%) than in control subjects (17.66%; OR 0.76, 95% CI 0.66–0.88, p < 0.001). Our results indicate a robust protective effect of PARK16 in Han Chinese PD patients. Functional approaches are needed to elucidate the effects of these SNPs on the regulation of gene expression.     

Correlation between LSP1 polymorphisms and the susceptibility to breast cancer

Objective: The present study aimed at assessing the relationship between Leukocyte-specific protein 1 gene (LSP1) polymorphisms (rs569550 and rs592373) and the pathogenesis of breast cancer (BC). Methods: 70 BC patients and 72 healthy subjects were enrolled in the study. Rs569550 and rs592373 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratio (OR) with 95% confidence interval (CI) were calculated by the chi-squared test to assess the relationship between LSP1 polymorphisms and BC risk. Linkage disequilibrium (LD) and haplotypes were also analyzed by HaploView software. Results: Genotype distribution of the control was in accordance with Hardy-Weinberg equilibrium (HWE). The homozygous genotype TT and T allele of rs569550 could significantly increase the risk of BC (TT vs. GG: OR=3.17, 95% CI=1.23-8.91; T vs. G: OR=1.63, 95% CI=1.01-2.64). For rs592373, mutation homozygous genotype CC and C allele were significantly associated with BC susceptibility (CC vs. TT: OR=4.45, 95% CI=1.38-14.8; C vs. T: OR=1.70, 95% CI=1.03-2.81). LD and haplotypes analysis of rs569550 and rs592373 polymorphisms showed that T-C haplotype was a risk factor for BC (T-C vs. G-T: OR=1.74, 95% CI=1.04-2.92). Conclusion: LSP1 rs569550 and rs592373 polymorphisms are both risk factors for BC.     

Polymorphisms in the 5' region of the CD14 gene are associated with eczema in young children

BACKGROUND: Variants in the CD14 gene (CD14) are hypothesized to be associated with atopic disorders. However, most studies have only investigated one polymorphism in this gene. OBJECTIVE: We sought to study the association of 5 single nucleotide polymorphisms (SNPs) in the 5' flanking region of CD14 with eczema and serum IgE levels in young children. METHODS: We genotyped 5 SNPs in an approximately 6.5-kb region in the 5' region of CD14 in 344 2-year-old white children from 2 birth cohorts in the northeastern United States. We examined the relation of both single SNPs and haplotypes in CD14 with the atopic outcomes. RESULTS: Two SNPs were significantly associated with eczema. In dominant models adjusted for potential confounders, SNP rs2569193 was associated with significantly decreased risk for eczema (odds ratio [OR] for CT/TT vs CC, 0.5; 95% CI, 0.3-0.8), whereas SNP rs2569190 (also reported as the C-159T) was associated with significantly increased risk for eczema (OR for CT/TT vs CC, 2.3; 95% CI, 1.4-3.8). The CT/TT genotypes of SNP rs2569190 also had higher geometric means of serum IgE than the CC genotype (24.6 vs 15 IU/mL, P = .025). Haplotype analyses provided results similar to those of the single SNP analyses. CONCLUSIONS: Our results contradict previous reports that have found a protective effect of the T allele of SNP rs2569190 (C-159T) against atopic disorders. Nevertheless, these results confirm the importance of polymorphisms in CD14 in the development of atopy, and future studies of this gene region will need to account for linkage disequilibrium and environmental exposures unique to the study population.     

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.     

Association of functional GITR gene polymorphisms related to expression of glucocorticoid-induced tumour necrosis factor-receptor (GITR) molecules with prognosis of autoimmune thyroid disease

The glucocorticoid-induced tumour necrosis factor (TNF)-receptor (GITR) affects the functions of regulatory T (T(reg)) and effector T (T(eff)) cells, but the significance of this phenomenon is still unclear. To examine the association of single nucleotide polymorphisms (SNPs) in the GITR gene with the expression of GITR molecules on T cells and with the pathological conditions in patients with autoimmune thyroid disease (AITD), we examined the frequencies of four candidate SNPs in AITD patients and healthy volunteers by restriction enzyme analysis and direct sequence analyses. We also analysed the GITR expression on peripheral T(reg) and T(eff) cells in AITD patients by three-colour flow cytometry. The CC genotype in the rs3753348 C/G SNP was significantly more frequent in patients with mild Hashimoto's disease (HD) than in those with severe HD [P = 0·0117, odds ratio (OR) = 3·13]. The AA genotype in the rs2298213 A/G SNP was significantly more frequent in patients with mild HD than in patients with severe HD (P = 0·010, OR = 4·43). All patients and healthy individuals had the GG genotype in rs60038293 A/G and rs11466696 A/G SNPs. The proportions of GITR(+) cells in T(reg) and T(eff) cells were significantly higher in AITD patients with the CC genotype of the rs3753348 SNP than in those with the GG genotype (P = 0·004 and P = 0·011, respectively). In conclusion, the rs3753348 C/G SNP in the GITR is associated with HD prognosis and expression on T(reg) and T(eff) cells.     

Association between miRNA-146a rs2910164 (G/C) polymorphism with the susceptibility to chronic HBV infection and spontaneous viral clearance in an Iranian population

Hepatitis B virus (HBV) infection is one of the clinical dilemmas in chronic liver diseases. MicroRNAs (miRNAs) are small noncoding RNA molecules that play an important role in the pathogenesis of liver diseases and single nucleotide polymorphisms (SNPs) in miRNA genes affect the clinical course of HBV infection. Previous studies have shown that miRNA-146a rs2910164 polymorphism can be associated with the pathogenesis of liver diseases such as hepatocellular carcinoma. The present study investigated the association between miRNA-146a rs2910164 polymorphism and susceptibility to HBV infection in an Iranian population. The study comprised 266 patients with chronic HBV infection, 172 patients with spontaneous viral clearance (SVC) after acute HBV infection, and 266 healthy control adjusted for sex and age. The genotyping of the miRNA-146a rs2910164 polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our data revealed that GG genotype and G allele of miRNA-146a rs2910164 SNP is dominated (P < 0.001) in patients with chronic HBV infection (Odds ratio [OR] = 3.92; 95% confidence interval [CI] = 2.1-7.32). miRNA-146a rs2910164 polymorphism showed a statistically significant association (P < 0.001) between CC genotype and allele C with SVC (OR = 2.92; 95% CI = 1.56-546). Our findings suggest miRNA-146a SNP (C/G) in our population may be associated with the susceptibility to HBV infection and CC genotype is associated with SVC. Also, the GG genotype and G allele at miRNA-146a rs2910164 is associated with chronic HBV infection in our population.     

RET基因调控区遗传变异与先天性巨结肠患病风险研究

目的先天性巨结肠（HSCR）是一种复杂的先天性疾病,RET是其主要的易感性基因。本研究对RET非编码区单核甘酸多态性（SNP）-5G〉A（rs10900296）,-1A〉C（rs10900297）和intron1 C〉T（rs2435357）进行分型分析,评估RET基因调控区SNPs及单倍型与先天性巨结肠之间的相关性。方法选取115名病例组病人和139名对照组正常人群,应用聚合酶链反应（PCR）技术和直接测序的方法进行基因分型。回归模型中使用OR值和95%置信区间（CI）作为基因型危险性的评价指标。结果 -5G〉A,-1A〉C,intron1C〉T各基因型频率在病例和对照人群的分布具有显著差异。-5 AA（OR=6.26,95%CI=3.62-10.83）,-1 CC（OR=7.54,95%CI=2.06-27.66）和intron1 TT（OR=19.22,95% CI=7.54-48.99）基因型均能显著增加HSCR发病的风险。单倍型A-C-T（OR=6.28,95% CI=3.77-10.46）和双体型A-C-T/A-C-T（OR=13.62,95% CI=3.48-53.30）分析同样表明与HSCR发病风险存在较强的相关性,并呈现出一定的累积效应。结论 RET基因调控区的基因多态性可能与HSCR的发病易感性有关,支持RET通路的常见变异在HSCR的发展过程中起着重要的作用的假设。     

Lack of association of polymorphism in miRNA-196a2 with Parkinson's disease risk in a Chinese population

MicroRNAs (miRNAs) are a new class of non-protein coding RNA molecules, which participate in diverse biological pathways. We hypothesized that miRNA-196a2 polymorphism is associated with the risk of Parkinson's disease (PD) in a Chinese population. In a case-control study of 549 PD patients and 736 control subjects frequency matched by age and gender, we genotyped the single-nucleotide polymorphism (SNP) rs11614913 (T>C) in miRNA-196a2, whose target mRNA was alpha-synuclein, and assessed its association with risk of PD by TaqMan Genotyping method. No association was found for the miR-196a2 rs11614913 CT/CC genotype (odds ratio (OR), 0.879, 95% confidence interval (CI), 0.681-1.135 for CT genotype; OR, 1.085, 95% CI, 0.793-1.484 for CC genotype) with risk of PD, compared with the TT genotype. These results suggest that SNP rs11614913 in miRNA-196a2 may not contribute to the susceptibility to PD.     

Association of ALOX5AP gene single nucleotide polymorphisms and cerebral infarction in the Han population of northern China

ABSTRACT: BACKGROUND: To explore the association of ALOX5AP single nucleotide polymorphisms (SNPs) and haplotype with the occurrence of cerebral infarction in the Han population of northern China. METHODS: Blood samples were collected from 236 patients of Han ancestry with a history of cerebral infarction and 219 healthy subjects of Han ancestry with no history of cerebral infarction or cardiovascular disease. Applied Biosystems(R) TaqMan(R) SNP Genotyping Assays for SNP genotyping were used to determine the genotypes of 7 ALOX5AP SNP alleles (rs4073259, rs4769874, rs9315050, rs9551963, rs10507391, rs9579646, and rs4147064). RESULTS: One SNP allele (A) of rs4073259 was significantly associated with development of cerebral infarction (P = 0.049). In comparison to control groups, haplotype rs9315050&rs9551963 AAAC [OR (95 % CI) =1.53 (1.02-2.29)], and genotypes rs4147064 CT [OR (95 % CI) =1.872 (1.082-3.241)], and rs9551963 AC [OR (95 % CI) = 2.015 (1.165-3.484)] increased the risk of cerebral infarction in patients with hypertension. Genotype rs9579646 GG [OR (95 % CI) = 2.926 (1.18-7.251)] increased the risk of, while rs4073259 GG [OR (95 % CI) = 0.381 (0.157-0.922)] decreased the risk of cerebral infarction in patients with diabetes. CONCLUSION: These results suggest the ALOX5AP SNP A allele in rs4073259 and genotype rs9579646 GG, rs9551963 AC, and haplotype rs9315050 & rs9551963 AAAC were associated with an increased risk of ischemic stroke in the Han population, while rs4073259 GG was associated with a decreased risk.     

Impact of Intercellular Adhesion Molecule-1 Genetic Polymorphisms on Coronary Artery Disease Susceptibility in Taiwanese Subjects

The principal pathogenesis of coronary artery disease (CAD) is coronary artery atherosclerosis, a chronic inflammatory disease of the vessel walls of the coronary artery. Intercellular adhesion molecule-1 (ICAM-1) displays an important role in the development of the inflammation reaction and atherosclerosis. Few studies report the association of ICAM-1 genetic polymorphisms with CAD in Taiwanese subjects. Therefore, we conducted a study to associate the single nucleotide polymorphisms (SNPs) of ICAM-1, rs5491, rs5498, rs281432 and rs3093030 with CAD. Five hundred and twenty-five male and female subjects, who received elective coronary angiography in Taiwan Chung Shan Medical University Hospital, were recruited to determine four ICAM-1 SNPs by real time-polymerase chain reaction and genotyping. The relationships among ICAM-1 SNPs, haplotypes, demographic and characteristics and CAD were analyzed. This study showed that rs281432 (C8823G) was the only ICAM-1 SNP which affect the development of CAD. Multivariate analysis revealed that ICAM-1 SNP rs281432 CC/CG [p=0.016; odds ratio (OR): 2.56, 95% confidence interval (CI): 1.19-5.56], male gender (p=0.018; OR: 1.66, 95% CI: 1.09-2.51), aspirin use in the past 7 days (p=0.001; OR: 2.05, 95% CI: 1.33-3.14), hypertension (p<0.001; OR: 2.15, 95% CI: 1.42-3.25), serum cardiac troponin I elevation (p<0.001; OR: 2.14, 95% CI: 1.47-3.24) and severe angina in recent 24 hours (p=0.001; OR: 1.97, 95% CI: 1.31- 2.95) increase the risk of CAD. In conclusion, ICAM-1 SNP rs281432 is an independent factor to predict the development of CAD. ICAM-1 SNP rs281432 homozygotic mutant GG can reduce the susceptibility to the CAD in Taiwanese subjects.