Analysis of Interleukin-8 Gene Variants Reveals Their Relative Importance as Genetic Susceptibility Factors for Chronic Periodontitis in the Han Population

Interleukin (IL)-8, an important chemokine that regulates the inflammatory response, plays an important role in periodontitis. Previous studies indicate that certain IL-8 gene polymorphisms are associated with periodontitis susceptibility in some populations. However, the literature is somewhat contradictory, and not all IL-8 polymorphisms have been examined, particularly in Han Chinese individuals. The aim of this study was to investigate the association of every IL-8 SNP with chronic periodontitis in Han Chinese individuals. We analyzed 23 SNPs with minor allele frequency (MAF)≥0.01, which were selected from 219 SNPs in the NCBI dbSNP and preliminary HapMap data analyses from a cohort of 400 cases and 750 controls from genetically independent Han Chinese individuals. Single SNP, haplotype and gender-specific associations were performed. We found that rs4073 and rs2227307 were significantly associated with chronic periodontitis. Further haplotype analysis indicated that a haplotype block (rs4073-rs2227307-rs2227306) that spans the promoter and exon1 of IL-8 was highly associated with chronic periodontitis. Additionally, the ATC haplotype in this block was increased 1.5-fold in these cases. However, when analyzing the samples by gender, no significant gender-specific associations in IL-8 were observed, similar to the results of haplotype association analyses in female and male subgroups. Our results provide further evidence that IL-8 is associated with chronic periodontitis in Han Chinese individuals. Furthermore, our results confirm previous reports suggesting the intriguing possibilities that IL-8 plays a role in the pathogenesis of chronic periodontitis and that this gene may be involved in the etiology of this condition.     

Replication Study Confirms Link between TSPAN18 Mutation and Schizophrenia in Han Chinese

Schizophrenia (SCZ) is a severe psychiatric disorder associated with many different risk factors, both genetic and environmental. A recent genome-wide association study (GWAS) of Han Chinese identified three single-nucleotide polymorphisms (SNPs rs11038167, rs11038172, and rs835784) in the tetraspanins gene TSPAN18 as possible susceptibility loci for schizophrenia. Hoping to validate these findings, we conducted a case-control study of Han Chinese with 1093 schizophrenia cases and 1022 healthy controls. Using the LDR-PCR method to genotype polymorphisms in TSPAN18, we found no significant differences (P>0.05) between patients and controls in either the allele or genotype frequency of the SNPs rs11038167 and rs11038172. We did find, however, that the frequency of the ‘A’ allele of SNP rs835784 is significantly higher in patients than in controls. We further observed a significant association (OR  = 1.197, 95%CI  = 1.047–1.369) between risk for SCZ and this ‘A’ allele. These results confirm the significant association, in Han Chinese populations, of increased SCZ risk and the variant of the TSPAN18 gene containing the ‘A’ allele of SNP rs835784.     

ZBTB40基因与中国汉族人群和美国高加索人群骨密度的关联研究

最近的全基因组关联研究发现ZBTB40(zinc finger and BTB domain containing 40)基因是一个潜在的调节骨密度的新基因,为了可靠地验证该基因与骨密度的关联关系,采用精细定位关联研究来检测ZBTB40基因内及其附近的SNPs与骨密度的关系.首先在中国样本(1 627个不相关的汉族样本)和美国样本(2 286个不相关高加索样本)中对ZBTB40基因的50个SNPs进行基因分型,然后采用Plink软件检测ZBTB40基因与腰椎和髋部骨密度的关联关系.证实了以前报道的SNPs rs7524102与腰椎和髋部骨密度的关联关系.另外还发现5个SNPs(rs10917209、rs6426748、rs4433361、rs3856183和rs7550872)与腰椎和髋部骨密度相关联.其中最显著的SNP是位于ZBTB40基因上游区域的rs6426748,其与腰椎骨密度的关联P值为9.82×10-4,多重检验校正后仍然显著.连锁不平衡分析表明rs6426748与rs10917209,rs7524102和rs7550872呈现高度连锁关系,位于长度为27 kb的单体型块内,因此ZBTB40基因的功能致病位点可能是rs6426748或该单体型块内某一未分型的SNP.     

SLC30A8 (ZnT8) variations and type 2 diabetes in the Chinese Han population

In recent genome-wide association studies, variants in the SLC30A8 gene have been found to be associated with risk for type 2 diabetes. We examined a possible association of tag SNPs spanning SLC30A8 and their haplotypes with type 2 diabetes in the Chinese Han population. There were 1508 Chinese Han type 2 diabetes patients and 1500 age- and gender-matched control subjects; all were genotyped for three tagging SNPs (rs2466295, rs4876703, and rs11558471) of the human SLC30A8 gene. The AA genotype of rs11558471 was found significantly more frequently in type 2 diabetes patients than in controls (46 vs 24%). The frequency of the A-C-A haplotype was significantly higher in type 2 diabetes patients than in controls (0.331 vs 0.120). The frequency of the A-C-G haplotype was significantly lower in type 2 diabetes patients than in controls (0.160 vs 0.365). We conclude that type 2 diabetes is associated with the AA genotype of rs11558471 in the human SLC30A8 gene. The A-C-A haplotype appears to be a risk factor and the A-C-G haplotype may be a protective factor against type 2 diabetes in Chinese Han.     

PPARGC1A基因Thr394Thr/Gly482Ser多态性与2型糖尿病的关联研究

对344例2型糖尿病患者和307名正常人的PPARGC1A基因单核苷酸多态性rs2970847(Thr394Thr)和rs8192678(Gly482Ser)与2型糖尿病的关系进行了单标记和单体型关联分析以及Logistic回归分析。在单标记分析中,对照组与病例组Thr394Thr的基因型和等位基因频率有显著差异(基因型, P =0.006; 等位基因, P < 0.001); Logistic回归和单体型分析表明, Thr394Thr的AA基因型及Thr394(ACA)-Ser482单体型增加患2型糖尿病的风险。Gly482Ser的基因型和等位基因频率在对照组与病例组间无显著差异。PPARGC1A基因是湖北汉人的一个2型糖尿病易感基因。     

4q22.1 Contributes to Bone Mineral Density and Osteoporosis Susceptibility in Postmenopausal Women of Chinese Han Population

Osteoporosis is a multifactorial disease in which genetic determinants are modulated by hormonal, environmental and nutritional factors. An important clinical risk factor in the pathogenesis of osteoporosis is the presence of genetics polymorphism in/around susceptibility genes/regions. This study explored whether the region of 4q22.1, which confers risk of developing osteoporosis in some populations, associated with bone mineral density and osteoporosis susceptibility in postmenopausal women of Han Chinese. We investigated 32 SNPs with minor allele frequencies ≥0.05 between 20 kb upstream and 20 kb downstream (40 kb window) of rs6532023, mapping in the 4q22.1 region, which was reported to be significantly associated with osteoporosis in previous studies. We found that rs6532023 was significantly associated with bone mineral density and osteoporosis (corrected p = 0.015) in our sample, including 440 cases and 640 controls, and allele G was supposed as a risk factor while T worked as a protective factor. Further genotype association analyses suggested a similar pattern (corrected p = 0.040). Additionally, analyses by haplotypes indicated that a haplotype block rs7683315-rs6532023-rs1471400-rs1471403 in the region associated with bone mineral density and osteoporosis (global p = 0.032), and risk haplotype A-G-G-C had almost 1.5-fold increased in the cases. To our knowledge, this is the first report to examine 4q22.1 region polymorphisms and osteoporosis in Han Chinese. Our results provide further evidence for an effect of the region of 4q22.1 on the etiology of osteoporosis and suggest that 4q22.1 may be a genetic risk factor for bone mineral density and osteoporosis.     

Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

BackgroundAtrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene.MethodsA total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study.ResultsIn single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared ‘TT’ haplotype with the common ‘TC’ haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with ‘TC’, carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with ‘TT’ haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF.ConclusionsVia a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor.     

骨质疏松症易感基因BDNF的遗传学关联分析及功能研究

为探索脑源性神经营养因子BDNF基因与中国汉族人群骨密度(bone mineral density, BMD)的关系,解析该基因调节骨质疏松症的功能机制,进而为中国汉族人群的骨质疏松症的防治提供依据。本研究从我国陕西地区征集了1300例汉族样本,并测量髋部/脊椎骨密度。选取BDNF基因上的14个标签SNPs进行基因分型,与1300例样本BMD进行关联分析,发现8个SNPs与髋部/脊椎BMD显著关联(P < 0.05)。其中,SNP rs16917237同时与髋部和脊椎骨密度关联,经Bonferroni校正后仍表现出显著性(0.05/14 = 0.0036)。整合连锁不平衡和单体型分析、表观功能注释、表达数量基因座分析、代谢通路分析进一步探索BDNF基因调节骨质疏松症的机制。构建小鼠前成骨细胞系(MC3T3-E1)人骨形态形成蛋白(rhBMP-2)诱导分化模型,利用小干扰RNA(siRNA)敲除BDNF。结果显示：14个SNPs位于同一单体型内;rs16917237在成骨细胞中表现出较强的激活型组蛋白H3K4me1、H3K4me3、H3K27ac修饰信号以及P300结合信号,表明其在成骨细胞中可能具有调控活性;rs16917237在11个组织中均能显著影响BDNF基因表达;BDNF基因位于与成骨细胞增殖分化相关的MAPK通路中;BDNF敲低能够显著降低MAPK通路中与成骨分化相关的CREB 基因mRNA和蛋白表达水平,提示其可能通过调控CREB表达进而影响成骨分化。生物信息学分析和功能实验结果一致,表明BDNF基因可能是影响骨质疏松症的重要功能基因。     

A tagging SNP in <Emphasis Type="Italic">ALOX5AP</Emphasis> and risk of stroke: a haplotype-based analysis among eastern Chinese Han population

A genome-wide approach found significant association of two at-risk haplotypes (HapA, HapB) in the ALOX5AP gene with myocardial infarction and stroke. To date, it is still controversial whether ALOX5AP gene polymorphisms are risk factors for stroke. The aim of the present study is to investigate the association between the ALOX5AP gene polymorphism and the risk for stroke in Eastern Chinese Han population with a haplotype-based analysis. We conducted a comprehensive association study of 507 stroke patients and 510 healthy controls to assess the association between the ALOX5AP tagging single-nucleotide polymorphisms (tSNPs) and stroke risk. Genotyping was performed using the PCR–RFLP assay. In the single-locus analysis, we found that the rs9579646 AG genotype was associated with a marginally decreased risk for stroke (adjusted odds ratio, 0.65; 95% confidence interval, 0.45–0.96), compared with the AA genotype. Haplotype-based association analysis of block 2 involving rs10507391 and rs12429692 revealed that the decreased risk of stroke was significantly associated with haplotype AA (OR, 0.66; 95% CI, 0.46–0.95). These results suggested that the genetic variants in ALOX5AP might modulate the risk of stroke in Eastern Chinese Han population. The frequencies of single-marker alleles and haplotypes showed remarkable differences from those in other populations.     

Association study of CRP gene polymorphism and hypertension in Han Chinese population

Background

Serum C-reactive protein (CRP) and genetic variation of CRP gene have been reported as a strong, independent predictor of myocardial infarction and stroke. But there is rare association evidence of CRP genetic variation and hypertension (HT).

Methods

A community-based case–control study including 1331 cases with HT and 1400 controls was used to evaluate the association of tagSNPs covered CRP gene, CRPP1 gene and 40 kb upstream with HT in a Chinese Han population. Haplotypes and stratification analysis were applied to further evaluate relationships between the screened SNPs and HT and general linear model (GLM) was applied to compare blood pressure levels between genotypes.

Results

In stage 1, five SNPs had positive association with HT (P < 0.05) and entered stage 2 and two SNPs rs876537 and rs10737175 polymorphisms showed significant association with HT in joint sample. Haplotype analysis showed that comparing with common haplotype T–C which was constructed by rs6677719 and rs10737175, haplotype T–T significantly associated with HT after adjusted covariates. Stratification analysis found significant associations of HT for rs876537, rs2808630, rs6677719 and rs10737175 in ≥ 50 years group, rs876537, rs10737175 in female, rs876537 and rs10737175 in non-smoking and non-drinking populations as well as rs2808630 in non-drinking population. Furthermore, quantitative trait analysis indicated significant differences of SBP and DBP between the genotypes of rs10737175, rs876537 and rs2808630 in non-treatment hypertensive cases and control population.

Conclusions

The findings of this study support that CRP gene polymorphisms have significant association with genetic susceptibility of HT and quantitative traits of blood pressure.     

Association of OX40L Polymorphisms with Sporadic Breast Cancer in Northeast Chinese Han Population

OX40L is an important costimulatory molecule that plays a crucial role in the regulation of T-cell-mediated immunity. The interaction of OX40-OX40L is involved in the pathogenesis of multiple autoimmune and inflammatory diseases such as systemic lupus erythematosus (SLE), carotid artery disease and cancer. The genetic variants of OX40L can increase the risk of SLE, atherosclerosis, systemic sclerosis and show gender-specific effects in some studies. Accordingly, we performed a case-control study including 557 breast cancer patients and 580 age- and sex-matched healthy controls to investigate whether single nucleotide polymorphisms (SNPs) in the OX40L gene are associated with sporadic breast cancer susceptibility and progression in Chinese Han women. Seven SNPs of OX40L (rs6661173, rs1234313, rs3850641, rs1234315, rs12039904, rs844648 and rs10912580) were genotyped with the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results indicated that rs3850641G allele could increase the susceptibility to breast cancer (P = 0.009662), even in the validation study (P = 0.0001515). A significant association between rs3850641 and breast cancer risk was observed under the additive model and dominant model (P = 0.01042 and 0.01942, respectively). The haplotype analysis showed that haplotype A_rs844648A_rs10912580 was significantly associated with breast cancer, even after 10,000 permutations for haplotypes in block only (P = 0.0003). In clinicopathologic features analysis, the association between rs1234315 and C-erbB2 status was significant (P = 0.02541). Our data primarily indicates that rs3850641 of OX40L gene contributes to sporadic breast carcinogenesis in a northeast Chinese Han population.     

Association of ATM and BMI‐1 genetic variation with breast cancer risk in Han Chinese

We tested the hypothesis that genetic variation in ATM and BMI‐1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer‐free controls of Han nationality. This was an observational, hospital‐based, case–control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy‐Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene were significantly higher in cases than in controls (P = .005, <.001 and .001, respectively). Two variants, rs1042059 and rs201024480, in BMI‐1 gene were low penetrant, with no detectable significance. After adjustment, rs189037 and rs1801516 were significantly associated with breast cancer under the additive model (OR: 1.37 and 1.52, 95% CI: 1.10‐1.71 and 1.14‐2.04, P: .005 and .005, respectively). In haplotype analysis, haplotypes A‐C‐G‐G (in order of rs189037, rs3092856, rs1801516 and rs373759) and A‐C‐A‐A in ATM gene were significantly associated with 1.98‐fold and 6.04‐fold increased risk of breast cancer (95% CI: 1.36‐2.90 and 1.65‐22.08, respectively). Nomogram analysis estimated that the cumulative proportion of 3 significant variants in ATM gene was about 12.5%. Our findings collectively indicated that ATM gene was a candidate gene in susceptibility to breast cancer in Han Chinese.     

Association of G72/G30 with schizophrenia in the Chinese population

Recently, the G72 gene was reported to be associated with schizophrenia in the French Canadian and Russian populations. Here, we report the results obtained from the study of six single-nucleotide polymorphisms (SNPs: rs3916965, rs3916967, rs2391191, rs1935062, rs778293, and rs3918342), which span an 82-kb region covering the complementary DNA sequences of G72 and G30, in 537 schizophrenia cases and 538 controls of the Han Chinese. In this work, we have identified statistically significant differences in allele distributions of two markers rs3916965 (P = 0.019) and rs2391191 (P = 0.0010), and a highly significant association between haplotype AGAC of the G72/G30 locus (P = 1.7 x 10(-4)) and schizophrenia. Our data provide further evidence that markers of the G72/G30 genes are associated with schizophrenia in a non-Caucasian population.     

Haplotype analysis of the CYP2J2 gene associated with myocardial infarction in a Chinese Han population

The cytochromes P450 epoxygenases CYP2J2 synthesize epoxyeicosatrienoic, which regulate endothelial function. The aim of this study was to assess the association between the human CY2J2 gene and myocardial infarction (MI) in a Chinese population using a haplotype‐based case–control study. There were 440 Chinese Han MI patients and 440 age‐matched control subjects genotyped for three SNPs (rs2271800, rs11572223, and rs14493270) of the human CYP2J2 gene. Haplotypes were constructed and their frequencies compared between the MI patients and the controls. The CC genotype of rs2271800 was found more frequently in the MI group than in the control group (p = 0.004). The frequency of the C–C–G haplotype was significantly higher in MI patients than in control subjects (p < 0.001). The present results indicate that MI is associated with the CC genotype of rs2271800 in the human CYP2J2 gene. The C–C–G haplotype appears to be a useful genetic marker of MI in Chinese Han people. Copyright © 2010 John Wiley & Sons, Ltd.     

云南汉族酒精依赖综合征与COMT遗传多态性的关联研究

目的：研究儿茶酚胺氧位甲基转移酶（COMT）的不同基因型及等位基因频率在云南汉族酒精依赖综合征患者组和健康对照组的分布差异。方法：应用聚合酶链式反应．限制性片段长度多态性分析法,对COMT基因的rs2075507、rs737865、rs4680、rsl65599四个基因位点进行特异性扩增,限制性内切酶酶切分型。结果：上述4个候选基因中,COMT基因rs737865位点C／C基因型频率在健康对照组较酒依赖组高,其基因型分布在两组中有差异,且具有统计学意义（P〈0．05）。其余3个位点统计学分析均无显著性差异（P〉0．05）。单倍型分析：上述四个候选基因构建出12种主要单倍型（每种单倍型在对照组和酒依赖组中的频率至少有一个大于1％）,单倍型A—C—A—A有可能是云南汉族酒精依赖发生的一种危险因子（OR：2．865,P=0．003347）。连锁不平衡分析显示：云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁（D〉0．8）。结论：在云南汉族人群中,COMT基因rs2075507、rs4680和rs165599位点与酒依赖无关联性,rs737865C／C基因型可能是酒精依赖的保护因子,可能降低嗜酒的发生率。单倍型A-C-A-A有可能是云南汉族酒精依赖发生的一种危险因子。云南汉族人群中,COMT基因的rs2075507和rs737865之间存在着强连锁。     

Association pattern of interleukin-1 receptor-associated kinase-4 gene polymorphisms with allergic rhinitis in a Han Chinese population

Objective

Interleukin-1 receptor-associated kinase-4 (IRAK-4) encodes a kinase that is essential for NF-kB activation in Toll-like receptor and T-cell receptor signaling pathways, indicating a possible crosstalk between innate and acquired immunities. We attempted to determine whether the polymorphisms in the Interleukin-1 receptor-associated kinase-4 (IRAK-4) gene are associated with allergic rhinitis (AR) in the Han Chinese population.

Methods

A population of 379 patients with AR and 333 healthy controls was studied. Blood was drawn for DNA extraction and total serum immunoglobulin E (IgE). A total of 11 single nucleotide polymorphisms (SNPs) in IRAK-4 were selected and individually genotyped.

Results

Significant allelic differences between cases and controls were obtained for the SNP of rs3794262 in the IRAK-4 gene. In the stratified analysis for gender, two SNPs (rs4251431 and rs6582484) in males appeared as significant associations. Subgroup analysis for the presence of different allergen sensitivities displayed associations only in the house dust mite-allergic cohorts (rs3794262, rs4251481). None of the selected SNPs in IRAK-4 was associated with total IgE level. The haplotype analyisis indicated GCCTGCGA was significantly associated with AR. The SNP-SNP interaction information analysis indicated that the selected sets of polymorphisms had no synergistic effect.

Conclusions

Our findings did not support the potential contribution of the IRAK-4 gene to serum IgE levels. However, the results demonstrated a gender- and allergen-dependant association pattern between polymorphisms in IRAK-4 and AR in Chinese population.     

基于核心家系的EGR3基因与精神分裂症的关联研究

研究表明位于染色体8p21.3区域的EGR3(Early growth response 3)是精神分裂症(Schizophrenia)的重要易感基因,然而,仍有两个病例-对照研究未能验证上述发现。为了研究EGR3基因在我国患者中是否与疾病关联,文章在中国汉族的核心家系中选择EGR3基因座位上的5个SNPs位点(rs1996147、rs1877670、rs3750192、rs35201266和rs7009708)进行基因分型和传递不平衡检验(Transmission disequilibrium test,TDT)。结果表明遗传标记rs1996147和rs3750192分别显示出显著的传递不平衡(2>4.40,P<0.05)。在连锁不平衡分析中,由2个(rs3750192和rs35201266)、3个(rs1877670、rs3750192和rs7009708)以及4个(rs1996147、rs1877670、rs3750192和rs7009708)SNPs位点构建的单倍型均显示与精神分裂症显著性关联(2>7.10,整体P<0.05)。总之,EGR3基因与中国汉族人群精神分裂症遗传易感性相关,后续关于EGR3基因进一步的功能研究将会更好的帮助我们了解该基因在疾病病理学机制中的作用。     

Genetic variants in MARCO are associated with the susceptibility to pulmonary tuberculosis in Chinese Han population

Background

Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk.

Principal Findings

To specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32–2.05, p _corrected = 9.27E–5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (p _corrected = 0.0001 and 0.029, respectively).

Conclusions

Our study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis.     

基于核心家系的EGR3基因与精神分裂症的关联研究

研究表明位于染色体8p21.3区域的EGR3(Early growth response 3)是精神分裂症(Schizophrenia)的重要易感基因, 然而, 仍有两个病例-对照研究未能验证上述发现。为了研究EGR3基因在我国患者中是否与疾病关联, 文章在中国汉族的核心家系中选择EGR3基因座位上的5个SNPs位点(rs1996147、rs1877670、rs3750192、rs35201266和rs7009708)进行基因分型和传递不平衡检验(Transmission disequilibrium test, TDT)。结果表明遗传标记rs1996147和rs3750192分别显示出显著的传递不平衡(c²>4.40, P<0.05)。在连锁不平衡分析中, 由2个(rs3750192和rs35201266)、3个(rs1877670、rs3750192和rs7009708)以及4个(rs1996147、rs1877670、rs3750192和rs7009708)SNPs位点构建的单倍型均显示与精神分裂症显著性关联(c²>7.10, 整体P<0.05)。总之, EGR3基因与中国汉族人群精神分裂症遗传易感性相关, 后续关于EGR3基因进一步的功能研究将会更好的帮助我们了解该基因在疾病病理学机制中的作用。