Association of the polymorphisms of chemokine genes (IL8, RANTES,MIG, IP10, MCP1 and IL16) with the pathogenesis of autoimmune thyroid diseases

Chemokines induce leukocyte chemotaxis and contribute to chronic inflammation. To clarify the association between functional polymorphisms in genes encoding some chemokines and the pathogenesis of Autoimmune thyroid disease (AITD), we genotyped IL8 ?251T/A, Regulated upon Activation, Normal T cell Expressed and presumably Secreted (RANTES)???403G/A, ?28C/G, MIG rs2276886G/A, IP10 ?1596C/T, Monocyte Chemoattractant Protein1 (MCP1)???2518G/A and IL16 ?295T/C polymorphisms. We genotyped these polymorphisms using the PCR-RFLP method in 149 Graves’ disease (GD) patients, including 59 patients with intractable GD and 53 patients with GD in remission, as well as 131 Hashimoto’s disease (HD) patients, including 54 patients with severe HD, 46 patients with mild HD and 99 healthy controls. The IL8 ?251TT genotype and MIG rs2276886 A allele were more frequent in patients with AITD (p?=?0.0139 and p?=?0.0005, respectively). The RANTES???403AA and ?28GG genotypes were less frequent in patients with AITD (p?=?0.0164 and p?=?0.0221, respectively). The MCP1 ?2518GG genotype was more frequent in HD patients (p?=?0.0323). The MIG rs2276886 AG genotype was less frequent in patients with intractable GD (p?=?0.0051). Interestingly, the age of onset in GD patients with the RANTES???28CC genotype was younger than in those with ?28CG and GG genotypes (p?=?0.0028). In this study, we first reported that the polymorphisms in IL8, RANTES and MIG genes are associated with the development of AITD, and that the MIG rs2276886 AG genotype is associated with the intractability of GD. The RANTES???28CC genotype is associated with young onset of GD.     

Association of functional polymorphisms in promoter regions of IL5, IL6 and IL13 genes with development and prognosis of autoimmune thyroid diseases

To clarify the association of genetic producibility of interleukin (IL)-5, IL-6 and IL-13, which are secreted by T helper type 2 (Th2), with the development and prognosis of autoimmune thyroid disease (AITD), we genotyped IL5-746C/T, IL6-572C/G and IL13-1112C/T polymorphisms, which are functional polymorphisms in the promoter regions of the genes regulating these cytokines. Fifty-seven patients with intractable Graves' disease (GD), 52 with GD in remission, 52 with severe Hashimoto's disease (HD), 56 with mild HD and 91 healthy controls were examined in this study. The IL13-1112T allele, which correlates with higher producibility of IL-13, was more frequent in patients with GD in remission than in those with intractable GD [P=0·009, odds ratio (OR)=3·52]. The IL5-746T allele, which may correlate with lower levels of IL-5, was more frequent in patients with GD in remission than controls (P=0·029, OR=2·00). The IL6-572G allele carriers (CG and GG genotypes), which have higher producibility of IL-6, were more frequent in AITD patients (P=0·033, OR=1·75), especially in GD in remission (P=0·031, OR=2·16) and severe HD (P=0·031, OR=2·16) than in controls. Interestingly, both allele and genotype frequencies of Th2 cytokine genes were similar between GD and HD patients. In conclusion, functional polymorphisms in the genes encoding Th2 cytokines are associated differently with the development and prognosis of AITD from each other.     

Polymorphisms in Th17-related genes and the pathogenesis of autoimmune thyroid disease

Abstract

The prognosis of autoimmune thyroid disease (AITD) including Graves’ disease (GD) and Hashimoto’s disease (HD) is difficult to predict. We previously suggested that Th17 cells may be associated with the pathogenesis of AITD. However, the association between gene polymorphisms in Th17-related genes and the prognosis of AITD was not clarified. To clarify this association, we genotyped 12 polymorphisms in 11 Th17-related genes (IL1Ra, IL6R, IL17R, IL21R, IL23R, CCR6, SOCS3, RORC, IL17A, IL17F and IL21) in 142?HD patients including 58 patients with severe HD and 48 patients with mild HD, 170 patients with GD including 81 patients with intractable GD and 49 patients with GD in remission, and 84 healthy volunteers. The frequency of the IL17F rs763780 T allele was higher in patients with severe HD than in patients with mild HD (p?=?.008). The frequency of the IL17R rs9606615 T allele was higher in patients with HD than in normal subjects (p?=?.011). The frequencies of the SOCS3 rs4969170 AA genotype, CCR6 rs3093024 AA genotype, and IL21 rs907715 AA genotype were higher in patients with intractable GD than in patients with GD in remission (p?=?.035, p?=?.002 and p?=?.030, respectively). In conclusion, IL17R rs9607715 and IL17F rs763780 polymorphisms are associated with the susceptibility and severity of HD, respectively. IL21 rs907715, SOCS3 rs4969170 and CCR6 rs3093024 polymorphisms are associated with the intractability of GD.     

Association between functional SIRT1 polymorphisms and the clinical characteristics of patients with autoimmune thyroid disease

Sirtuin1 (SIRT1) is a Class 3 nicotinamide adenine dinucleotide-dependent histone deacetylase (HDAC) that is thought to be implicated in the protection against autoimmune diseases. However, an association between SIRT1 and autoimmune thyroid disease (AITD) has not been reported. In this study, we selected four single nucleotide polymorphisms (SNPs) in the SIRT1 gene, rs12049646 T/C (termed SNP1), rs12778366 T/C (termed SNP2), rs3758391 T/C (termed SNP3), and rs4746720 T/C (termed SNP4). We genotyped each of these polymorphic sites in 185 patients with Graves’ disease (GD), including 76 patients with intractable GD and 57 patients with GD in remission; 151 patients with Hashimoto’s disease (HD), including 68 patients with severe HD and 54 patients with mild HD; and 96 healthy volunteers. SNP1 and SNP3 were genotyped by the PCR-RFLP method; SNP2 and SNP4 were genotyped using TaqMan® SNP genotyping assays. We also measured the levels of SIRT1 mRNA in CD4⁺ T cells from 18 control subjects, 16 patients with GD in remission and 14 patients with mild HD using a real-time PCR method. In patients with GD and HD, the C carriers (TC?+?CC genotypes) of SNP3 showed significantly higher titers of McAb than the TT genotype (p?=?0.0261 and p?=?0.0309, respectively). Additionally, the T carriers (TT?+?TC genotypes) of SNP4 showed significantly higher titers of McAb than the CC genotype in patients with GD (p?=?0.0079). In conclusion, the polymorphisms in the SIRT1 gene were associated with a greater production of thyroid autoantibodies.     

Polymorphisms and expression of genes encoding Argonautes 1 and 2 in autoimmune thyroid diseases

The microRNA (miRNA) biogenesis pathway is regulated by specific proteins and enzymes, including Dicer, Drosha, DGCR8, Exportin 5 and the Argonaute (AGO) family. In this study, we investigated the AGO family, which is the primary component of RISC (RNA-induced silencing complex) and directly binds to microRNA. We examined the association of polymorphisms in AGO family genes with AGO expression and with the development and prognosis of autoimmune thyroid diseases. We genotyped AGO1 rs636832A/G, AGO2 rs7005286C/T, AGO2 rs11166985A/G and AGO2 rs2292779C/G polymorphisms in 184 Graves’ disease (GD) patients, 195 Hashimoto’s disease (HD) patients and 122 healthy volunteers using the polymerase chain reaction-restriction fragment length polymorphism method. We also examined the expression of AGO1 and AGO2 mRNAs in peripheral blood mononuclear cells (PBMC) obtained from 52 GD patients, 41?HD patients, and 25 healthy volunteers using quantitative RT-PCR methods. The G allele of AGO1 rs636832 and the A allele of AGO2 rs11166985 polymorphisms were significantly more frequent in GD patients than in healthy controls. The A allele of AGO2 rs11166985 was also significantly more frequent in intractable GD patients than in controls. The C carrier (CC?+?CG genotypes) and C allele of AGO2 rs2292779 polymorphism were significantly more frequent in intractable GD patients than in patients with GD in remission. Expression of AGO1 mRNA in PBMC was significantly higher in AITD patient than in controls, and that of AGO2 mRNA in PBMC was significantly higher in intractable GD patients than in patients with GD in remission. Furthermore, the expression levels of both the AGO1 and AGO2 genes were significantly correlated with the proportions of Th17 cells in PBMC. In conclusion, the polymorphisms of the AGO1 and AGO2 genes, the expression levels of which correlated with the proportion of Th17 cells, were associated with the development and prognosis of GD. The AGO2 rs2292779 C carrier and C allele were associated with the intractability of GD.     

DNMT1和DNMT3B基因多态性与食管癌发病风险的关联分析

目的 探讨DNMT1基因多态性位点(rs16999593,rs2228611)和DNMT3B基因多态性位点(rs2424908)的基因型与食管癌及其病理参数的关联.方法 采用病例对照研究,使用MassARRAY检测技术对258例食管癌患者和260例健康对照的3个多态性位点基因型分布进行分析.采用Logistic回归模型分析各基因型与食管癌发生的关系并比较不同基因型与食管癌病理参数的关系.结果 DNMT1基因rs16999593位点TC基因型(OR =0.69,95％ CI:0.47～1.00)和rs2228611位点GA基因型(OR =0.67,95％ CI:0.46 ～0.98)与食管癌的低风险相关,rs16999593 TC、CC基因型与食管癌分化程度相关(中分化:TC vs.TT:OR =0.53,95％ CI:0.33 ～0.86;低分化:CC vs.TT:OR=2.79,95％ CI:1.12～6.91),rs2228611 GA基因型与高分化食管癌(GA vs.GG:OR=0.47,95％ CI:0.25 ～0.88)和无周围淋巴结转移(GA vs.GG:OR=0.62,95％ CI:0.39 ～0.98)有关,DNMT3B基因rs2424908 CC基因型与肿瘤Ⅲ～Ⅳ分期(CC vs.TT:OR=0.38,95％CI:O.15～0.92)及远端淋巴结转移(CC vs.TT:OR =0.18,95％ CI:0.40 ～0.80)相关.结论 本研究发现rs16999593和rs2228611位点与食管癌的发生及分化程度相关,rs2228611和rs2424908位点和淋巴结转移相关,rs2424908位点和肿瘤分期有相关性.     

DICER and DROSHA gene expression and polymorphisms in autoimmune thyroid diseases

Dicer and Drosha are RNase III enzymes that are necessary for the biogenesis of most miRNAs. However, there are no reports on the association of Dicer and Drosha with the pathogenesis of autoimmune thyroid disease (AITD). We genotyped DICER rs3742330A/G and rs1057035T/C as well as DROSHA rs644236C/T and rs10719C/T polymorphisms in 255?Hashimoto's disease (HD) patients, in 255 Graves' disease (GD) patients and in 128 healthy controls by the polymerase chain reaction (PCR)- restriction fragment length polymorphism (RFLP) method. We also examined the expression of DICER and DROSHA gene in peripheral blood mononuclear cells (PBMCs) by quantitative RT-PCR (qRT-PCR) methods. The TT genotype of the DICER rs1057035 polymorphism was less frequent in GD patients (p?=?0.0098) than in healthy subjects. The CC genotype of DROSHA rs644236 polymorphism were more frequent in GD patients than in HD patients (p?=?0.0171). The gene expression of DICER was lower in patients with AITD compared with that in control subjects (p?=?0.0064) and was lower in patients with GD in remission than in patients with intractable GD (p?=?0.0213). In addition, the expression of DROSHA was lower in patients with AITD than that in control subjects (p?p?=?0.0440). In conclusion, the DICER rs1057035 TT genotype and DROSHA rs644236?CC genotype were associated with the development of GD and the differentiation between GD and HD, respectively. The expression levels of DICER and DROSHA genes were low in AITD and differed depending on the intractability of GD and the severity of HD, respectively.     

The functional polymorphisms of VDR,GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases

Vitamin D is a multi-functional immune regulator, and a low serum concentration of vitamin D promotes autoimmune inflammation. In this study, we evaluate the association between the prognosis of autoimmune thyroid disease (AITD) and the functional polymorphisms of genes that regulate vitamin D metabolism. For 139 Graves’ disease (GD) patients, 116 Hashimoto''s disease (HD) patients and 76 control subjects, we genotyped the following polymorphisms using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP): vitamin D receptor (VDR): rs731236, rs7975232, rs2228570 and rs1544410; group-specific component (GC): rs7041 and rs4588; and CYP2R1: rs10741657. The frequency of the TT genotype for the rs731236 polymorphism was higher in GD patients than in HD patients (P = 0·0147). The frequency of the C allele for the rs7975232 polymorphism was higher in GD patients than in control subjects (P = 0·0349). The proportion of GD patients whose anti-thyrotrophin receptor antibody (TRAb) level was >51% was higher in those with the CC genotype than in those with the CA+AA genotypes (P = 0·0065). The frequency of the CC genotype for the rs2228570 polymorphism was higher in HD patients than in control subjects (P = 0·0174) and GD patients (P = 0·0149). The frequency of the Gc1Gc1 genotype for the GC polymorphism and the AG genotype for the CYP2R1 polymorphism were lower in intractable GD than in GD in remission (P = 0·0093 and 0·0268, respectively). In conclusion, genetic differences in the VDR gene may be involved in the development of AITD and the activity of GD, whereas the genetic differences in the GC and CYP2R1 genes may be involved with the intractability of GD.     

Association of the polymorphisms in the gene encoding thyroglobulin with the development and prognosis of autoimmune thyroid disease

Graves’ disease (GD) and Hashimoto’s disease (HD) are autoimmune thyroid diseases (AITDs), and the prognosis of AITDs is different for each patient. We examined the association of polymorphisms in the Thyroglobulin (TG) gene with the pathogenesis of AITD. We genotyped TG rs180195G/A, rs853326G/A, rs2076740C/T, rs2703013G/T, rs2958692C/T and rs733735A/G polymorphisms in 137?HD patients, 131 GD patients and 89 healthy controls and also examined the levels of TG mRNA expression and serum TG. The TG rs180195 GG genotype was more frequent in HD patients (p?=?.0277), and the proportion of CD4⁺ cells with high levels of TG mRNA was greater in individuals with the GG genotype than in A carriers (p?=?.0107). The TG rs2703013 TT genotype was less frequent in AITD (p?=?.0186), and serum TG levels were lower in individuals with the TT genotype than in G carriers (p?=?.0170). In the TG rs2958692 polymorphism, the T allele was more frequent in intractable GD than in GD in remission (p?=?.0055), and serum titres of anti-thyroglobulin antibody (TgAb) were lower in GD patients with the TT genotype than in C carriers (p?=?.0151). In the TG rs2076740 polymorphism, serum titres of TgAb were higher in HD patients who were T carriers than in those with the CC genotype (p?=?.0359). SNPs in the TG gene were associated with the development of HD and GD, the intractability of GD, and the levels of TG mRNA expression, serum TG, and serum TgAb.     

DNA甲基化、单核苷酸多态性与肿瘤

DNA甲基化是表观遗传修饰的重要部分,基因异常甲基化在肿瘤发生、发展中扮演重要角色.众多研究结果表明单核苷酸多态性(single nucleotide polymorphism,SNP)与DNA甲基化之间存在密切联系,可能通过改变甲基化位点或对DNA甲基化相关酶类产生影响,继而影响到相关基因的甲基化状态,改变表达水平,...     

Associations of single nucleotide polymorphisms in precursor-microRNA (miR)-125a and the expression of mature miR-125a with the development and prognosis of autoimmune thyroid diseases

It is important to search the biomarker to predict the development and prognosis of autoimmune thyroid diseases (AITDs) such as Hashimoto''s disease (HD) and Graves'' disease (GD). MicroRNA (miR) bind directly to the 3′ untranslated region of specific target mRNAs to suppress the expression of proteins, promote the degradation of target mRNAs and regulate immune response. miR-125a is known to be a negative regulator of regulated upon activation normal T cell expressed and secreted (RANTES), interleukin (IL)-6 and transforming growth factor (TGF)-β; however, its association with AITDs remains unknown. To clarify the association between AITDs and miR-125a, we genotyped the rs12976445 C/T, rs10404453 A/G and rs12975333 G/T polymorphisms in the MIR125A gene, which encodes miR-125a, using direct sequencing and polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) methods in 155 patients with GD, 151 patients with HD and 118 healthy volunteers. We also examined the expression of miR-125a in peripheral blood mononuclear cells (PBMCs) from 55 patients with GD, 79 patients with HD and 38 healthy volunteers using quantitative real-time PCR methods. We determined that the CC genotype and C allele of the rs12976445 C/T polymorphism were significantly more frequent in patients with HD compared with control subjects (P < 0·05) and in intractable GD compared with GD in remission (P < 0·05). The expression of miR-125a was correlated negatively with age (P = 0·0010) and down-regulated in patients with GD compared with control subjects (P = 0.0249). In conclusion, miR-125a expression in PBMCs and the rs12976445 C/T polymorphism were associated with AITD development and prognosis.     

PATZ1基因单核苷酸多态性与无精症的关系

目的 研究PATZ1基因的4个单核苷酸多态性(single nucleotide polymorphism,SNP)rs2240424、rs2057951、rs2240427和rs714909的多态性与无精症的关系.方法 用PCR-限制性片段长度多态性分析方法,在180例无精症患者和190名正常男性中对上述4个SNP位点的基因频率和基因型频率分布进行调查.结果 rs2057951位点的等位基因C(35.0%vs.27.6%,P=0.031)和带有等位基因C个体(CT+CC)(57.8%vs.46.3%,P=0.027)的频率在无精症患者显著高于正常男性.4种SNP的单倍型在两组人群中的分布差异有统计学意义(P=0.01),单倍型ACAC(11.1%vs.6.6%,P=0.029)和ACGC(11.2%vs.5.2%,P=0.003)在无精症患者中显著高于正常男性.结论 PTAZ1的rs2057951位点的等位基因C和单倍型ACAC和ACGC增加无精症的易感性,提示PTAZ1基因可能与无精症发病相关.     

DNMT3B mutations and DNA methylation defect define two types of ICF syndrome

ICF syndrome is a rare autosomal recessive disease characterized by variable immunodeficiency, centromeric instability, and facial abnormalities. Mutations in the catalytic domain of DNMT3B, a gene encoding a de novo DNA methyltransferase, have been recognized in a subset of patients. ICF syndrome is a genetic disease directly related to a genomic methylation defect that mainly affects classical satellites 2 and 3, both components of constitutive heterochromatin. The variable incidence of DNMT3B mutations and the differential methylation defect of alpha satellites allow the identification of two types of patients, both showing an undermethylation of classical satellite DNA. This classification illustrates the specificity of the methylation process and raises questions about the genetic heterogeneity of the ICF syndrome.     

Tumor necrosis factor receptor-associated factor 1 (TRAF1) polymorphisms and susceptibility to autoimmune thyroid disease

Former studies have revealed the link between the tumor necrosis factor (TNF) receptor-associated factor 1 (TRAF1) polymorphisms and autoimmunity. In the present study, we took an opportunity to investigate the association between TRAF1 and autoimmune thyroid disease (AITD) in order to find a new susceptibility gene. A total of 1029 AITD patients [677 Graves’ disease (GD) patients and 352 Hashimoto thyroiditis (HT) patients] and 899 controls were enrolled. We used matrix-assisted laser desorption ionization-time of flight mass spectrometer (MALDI-TOF-MS) to detect the polymorphisms of rs4836834, rs10760130, rs10818488, rs2239658, rs2900180. We also explored the association between polymorphisms and clinical subphenotypes. Genotype frequencies of the five loci in all AITD patients were significantly different from those of controls. Genotype frequencies of rs10760130, rs2239658 and rs2900180 in GD patients were significantly different from controls. Allele analysis found that T allele of rs4836834, G allele of rs10760130, A allele of rs10818488, T allele of rs2239658 and T allele of rs2900180 were significantly higher in GD and AITD patients. No significant differences were found between HT patients and controls. Haplotype analysis found three haplotypes including ACAGC, TTGAT and TCGAC. ACAGC frequencies were significantly lower in GD and HT patients. However, TTGAT frequency was only significantly higher in GD patients. No significant results were found between polymorphisms and clinical subphenotypes. Our study reveals TRAF1 as a susceptibility gene of AITD in Chinese Han population.     

DNMT3A对骨关节炎软骨细胞SOX9基因DNA甲基化修饰的影响

目的 探讨DNMT3A对SOX9基因DNA甲基化修饰的影响。方法 培养正常软骨细胞和OA软骨细胞,显微镜下观察软骨细胞形态,甲苯胺蓝染色、Ⅱ型胶原染色鉴定软骨细胞,qRT-PCR、Western Blot检测DNMT3A、SOX9 mRNA和蛋白表达水平,亚硫酸氢盐测序检测SOX9基因DNA甲基化状态,慢病毒沉默DNMT3A观察SOX9基因DNA甲基化修饰的变化。结果 正常软骨细胞形态规则,体积较大,数量较多,OA软骨细胞形态不规则,体积较小,数量较少。与正常软骨细胞比较,OA软骨细胞中DNMT3A mRNA和蛋白表达量增高（P＜0.05）,SOX9 mRNA和蛋白表达量明显降低（P＜0.05）,SOX9基因DNA甲基化百分比增高。在OA软骨细胞中沉默DNMT3A后,SOX9基因DNA甲基化百分比明显降低。结论 DNMT3A调节SOX9基因DNA甲基化修饰参与OA软骨细胞病变。     

The +869T/C polymorphism in the transforming growth factor-beta1 gene is associated with the severity and intractability of autoimmune thyroid disease

The severity of Hashimoto's disease (HD) and the intractability of Graves' disease (GD) vary among patients. To clarify whether the +869T/C polymorphism in the transforming growth factor-beta1 (TGF-beta1) gene, which is associated with TGF-beta1 expression, is involved in the intractability of GD and severity of HD, we genotyped the TGF-beta1 +869T/C polymorphism by polymerase chain reaction-restriction fragment length polymorphism method in genomic DNA samples from 33 patients with HD who developed hypothyroidism before they were 50 years old (severe HD) and 30 untreated, euthyroid patients with HD who were older than 50 years (mild HD). We also examined 48 euthyroid patients with GD who had been under treatment and were still positive for anti-thyrotropin receptor antibodies (intractable GD), 20 euthyroid patients with GD in remission and 45 healthy controls. The frequency of the T allele and the TT genotype were higher in patients with severe HD than in those with in mild HD. In contrast, the frequency of the CC genotype was higher in patients with intractable GD than in patients with GD in remission. In conclusion, the +869T/C polymorphism in the TGF-beta1 gene is associated with the severity and intractability of autoimmune thyroid disease.     

组织型激肽释放酶基因多态性与长沙地区汉族人群脑出血的关联研究

目的 分析长沙地区汉族人群脑出血与组织型激肽释放酶(kallikrein 1,KLK1)基因多态性的关系.方法 收集273例散发性脑出血患者和140名正常对照者的外周血标本.采用多重单碱基延伸单核苷酸多态分型技术和DNA测序法检测KLK1基因rs5516及rs5517多态性位点在两组人群中的分布.结果 (1)脑出血组及对照组KLK1基因rs5516多态和等位基因频率分布差异无统计学意义(P>0.05);脑出血组组织型KLK1基因rs5517多态A等位基因频率显著高于对照组(P<0.05).(2)对照组rs5517多态AA及GA基因型携带者舒张压水平显著高于GG基因型携带者(P<0.05);而rs5516位点各基因型亚组间血压水平差异无统计学意义(P>0.05).结论 组织型激肽释放酶基因rs5516多态性与脑出血无关,而组织型激肽释放酶基因rs5517多态性与脑出血存在关联,可能通过影响血压水平而参与脑出血的发生发展.     

Association of ATP-binding cassette transporter A1 gene polymorphisms with plasma lipid variability and coronary heart disease risk

Objective: Our study aimed to investigate the association of ABCA1 polymorphisms with plasma lipid variability and CHD risk in the Chinese Han population. Methods: 754 CHD patients and 760 controls were included in this case-control study. Three SNPs (rs363717, rs4149339, and rs4149338) in ABCA1 3’UTR and one nonsynonymous SNP (rs2230808) in ABCA1 exon 35 were selected and genotyped. The analysis of genetic data was performed using the SNPstats program and the SPSS17.0 software. Results: Significant associations were observed between SNP rs363717 and CHD risk under different genetic models before or after Bonferroni corrections (codominant model: OR = 0.70, P = 0.003 for AG vs. AA; dominant model: OR = 0.71, P = 0.003 for GG + AG vs. AA). The nonsynonymous SNP rs2230808 was associated with higher total cholesterol levels (P = 0.047). The GCC haplotype (consisting of alleles of SNPs rs363717, rs4149339, and rs4149338) was associated with a decreased risk of CHD (OR = 0.8, P = 0.027). Three ABCA1 SNPs interacted with high triglyceride levels to increase CHD risk (P values of interactions were 0.010 for rs363717, 0.010 for rs4149339, and 0.020 for rs4149338, respectively). Conclusions: Our results suggest that ABCA1 polymorphisms influence plasma lipid variability and CHD risk. ABCA1 polymorphisms could also modify the effects of plasma lipids on CHD risk.