Frequency Of A1 Allele Research Articles

Genetic polymorphisms of VKORC1, CYP2C9, CYP4F2 in Bai-, Zang-Chinese

This study aims to detect the popular polymorphisms in VKORC1, CYP2C9 and CYP4F2 in Bai-, Zang-Chinese, to start the exploration of better use of warfarin in Chinese minorities.Methods370 healthy, unrelated...

Synergistic effect of stromelysin-1 (matrix metalloproteinase-3) promoter (-1171 5A->6A) polymorphism in oral submucous fibrosis and head and neck lesions

BackgroundMatrix metalloproteinases (MMPs) are enzymes that degrade all the components of extra cellular matrix and collagen. Various types of MMPs are known to be expressed and activated in patients with oral submucous fibrosis (OSMF) as well as head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to asses the association of the single nucleotide polymorphism (SNP) adenosine insertion/deletion polymorphism (-1171 5A->6A) in the MMP-3 promoter region in these lesions.MethodsMMP-3 SNP was genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) analysis in a case control study consisting of 362 participants; 101 cases of OSMF, 135 of HNSCC and 126 controls, compared for age, sex and habits. ROC distribution was plotted to assess the contributions of genetic variation in MMP-3 genotypes with relation to age.ResultsAnalysis of MMP 3 (-1171 5A->6A) polymorphism revealed the frequency of 5A allele in OSMF, HNSCC and controls to be 0.15, 0.13 and 0.07, respectively. A significant difference was found in 5A genotype frequency between OSMF (5A genotype frequency = 0.15, p = 0.01, OR = 2.26, 95% CI = 1.22-4.20) and in controls (5A genotype frequency 0.07) as well as HNSCC (5A genotype frequency 0.13, p = 0.03,95%CI = 1.06-3.51) and controls (5A genotype frequency = 0.07) In this study, 5A genotype had greater than two fold risk for developing OSMF (OR = 2.26) and nearly the same in case of HNSCC (OR = 1.94) as compared to controls. In patients with OSMF as well as HNSCC, the ROC analysis between the MMP-3 genotype and age, 6A/6A allele was found to be significant in patients both over and under 45 years of age; while the 5A/5A carrier alleles showed an association only in patients less than 45 years of age.ConclusionsThis study concluded that the expression of MMP-3 genotype associated with the 5A alleles, it may have an important role in the susceptibility of the patients to develop OSMF and HNSCC.

Regulation of disease susceptibility and mononuclear cell infiltration into the labial salivary glands of Sjogren's syndrome by monocyte chemotactic protein-1

To investigate how monocyte chemotactic protein-1 (MCP-1) is involved in the pathological process of primary SS (pSS). Guanine (G) to adenine (A) single nucleotide polymorphism (SNP) of the -2518 MCP-1 promoter region in pSS and healthy controls was determined by the PCR-restriction fragment length polymorphism technique. Immunohistochemical staining towards MCP-1 and C-C motif chemokine receptor-2 (CCR2), a receptor of MCP-1, of the labial salivary glands of pSS was investigated. Furthermore, the expression of MCP-1 and CCR2 from the cultured primary salivary epithelial cells was studied by RT-PCR, ELISA and western blotting. The genotype and allele frequency of SNP of MCP-1 at -2518 showed that the G/G genotype is low but the presence of allele A as well as the A-allele frequency are high in pSS (n = 52) as compared with healthy controls (n = 164). Immunohistochemistry showed in situ expression of MCP-1 and CCR2 in the ductal structure and infiltrating mononuclear cells (MNCs) of patients with pSS. Primary salivary epithelial cells in vitro from pSS produced MCP-1, which was significantly stimulated by IFN-gamma, as identified by both ELISA and RT-PCR. In contrast to MCP-1, CCR2 expression of primary salivary epithelial cells in vitro was not so changed by IFN-gamma. MCP-1 is involved in the disease susceptibility of pSS in the Japanese population. MCP-1 interactions with CCR2, which may be facilitated by IFN-gamma, are thought to perpetuate MNC infiltration into the salivary glands of SS.

Dopamine D2 Receptor Genotype Is Associated with Increased Mortality at a 10-Year Follow-up of Alcohol-Dependent Individuals

Because the TAQ1 A1 allele may be associated with alcohol-related medical illnesses, and medical illnesses in alcohol-dependent individuals are associated with increased mortality, we test the hypothesis that the TAQ1 A1 allele of the DRD2 gene is associated with increased mortality in alcohol-dependent individuals. Following an index treatment episode, a 10-year follow-up study in 366 alcohol-dependent individuals was performed. The TAQ1 A1/A2 DRD2 genotype and allele frequencies were compared between those deceased and those still living at the 10-year point. In addition, the genotype and allele frequencies of these alcohol-dependent individuals were compared to that in 578 control subjects. The prevalence of the A1 allele differed between the deceased and living patients and the controls: 47% of the deceased were A1+, compared to 37% of the living patients and 32% of the controls. The frequency of the TAQ1 A1/A2 genotype also differed between the groups. Thus, 43% had the A1/A2 genotype in comparison with 32% in the living patients and 29% in the controls. The TAQ 1 A1 allele frequency differed between the groups. The frequency of A1 allele was 25% in the deceased patients compared to 21% in the living patients and 17% in the controls. The TAQ I A1 allele of the DRD2 gene (or DRD2 gene region) was associated with increased mortality over a 10-year period in alcohol-dependent individuals.

Associations of Protein Tyrosine Phosphatase Nonreceptor 22 (PTPN22) Gene Polymorphisms with Susceptibility to Graves' Disease in a Japanese Population

The polymorphism of the protein tyrosine phosphatase nonreceptor 22 (PTPN22) gene, which encodes an important negative regulator of T cell activation, has been reported to be associated with susceptibility to Graves' disease (GD) in Caucasians. The objective of this study was to investigate whether PTPN22 gene polymorphisms confer susceptibility to GD and Graves' ophthalmopathy (GO) in a Japanese population. We performed a case-control study of PTPN22 gene polymorphisms in Japanese GD patients (n = 414) and healthy control subjects with no antithyroid autoantibodies or family history of autoimmune disorders (n = 231). The G-1123C polymorphism (rs2488457) in the promoter region, Arg620Trp (C1858T) polymorphism (rs2476601) in exon 14, IMS-JST146695 polymorphism (rs3789607) in intron 19, and SNP37 (rs3789604) downstream of the PTPN22 gene were determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism using restriction enzymes and direct PCR sequencing methods. None of the GD patients or control subjects had the 1858T allele of the PTPN22 gene polymorphism. The AA-genotype and A-allele frequencies of SNP37 were significantly higher in GD patients than in control subjects (A-allele frequency: p = 0.0085, odds ratio = 1.45). The genotype frequencies and allele frequencies of the G-1123C and IMS-JST146695 polymorphisms did not differ between GD patients and control subjects. The -1123G/1858C/JST146695T/SNP37C haplotype frequency was significantly lower in GD patients than in control subjects. There were no associations between PTPN22 gene polymorphisms and GO. The results suggest that SNP37 of the PTPN22 gene is associated with susceptibility to GD in a Japanese population. Further studies including functional analyses are required.

Matrix metalloproteinase-3 gene polymorphism and dilatative pathology of ascending thoracic aorta

Matrix metalloproteinase-3 (MMP-3) degrades extracellular matrix and may lead to development of dilatative pathology of ascending thoracic aorta. Expression of MMP-3 depends upon the 5A/6A polymorphism in the promoter region. An increased number of 5A alleles leads to high expression of MMP-3. Thus, objective of the study was to determine whether the 5A/6A polymorphism in the promoter region of MMP-3 gene is associated with the development of dilatative pathology of ascending thoracic aorta. We studied 76 patients (age ranged from 31 to 81 years; median age, 64 years) who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n=604) aged 25-64 years, all from Lithuania. DNA was analyzed by using real-time polymerase chain reaction to genotype polymorphism 5A/6A at a position -1171 of the MMP3 gene promoter. The prevalence of MMP-3 genotypes was similar in the group of dilatative pathology of ascending thoracic aorta and random sample of population. The frequency of 5A allele did not differ significantly between both groups and was 0.506 and 0.514, respectively. Male carriers of 5A/5A genotype were significantly younger compared with those with the 6A/6A genotype. In conclusion, the frequency of MMP-3 promoter 5A/6A genotypes did not differ between the group of patients with dilatative pathology of ascending thoracic aorta and the random sample of population, but the males with dilatative pathology of ascending thoracic aorta and 5A/5A genotype required aortic reconstruction surgery at the younger age than the males carrying 6A/6A genotype in the MMP-3 promoter region.

Association between TGF-α gene BaraH I polymorphism and nonsyndromic cleft lip with or without cleft palate

Objective Nonsyndromic cleft lip with or without cleft palate(NSCL/P)is a common craniofacial birth defect which results in lifelong medical and social consequences.Although Asians have the highest birth prevalence of oral-facial clefts,the majority of gene mapping studies of cleft lip with or without cleft palate(CL/P)have been in European or Ameriean Caucasians.Therefore,the obiective of this study was to evaluate association between transforming growth factor alpha(TGF-α)gene BamH Ⅰ polymorphism and NSCL/P in Chinese.Methods 107 patients with NSCL/P and 136 healthy controls were examined for TGF-α/BamH Ⅰ genotypes.TGF-α/BamH Ⅰ typing was carried out by digesting the locus specific polymerase chain reaction amplified products with alleles specific BamH Ⅰ restriction enzyme(PCR-RELP).Resuits A1 allele frequency was 0.06 and A2 allele frequency was 0.94 in the controls.A1 allele frequency was 0.14 and A2 allele frequency was 0.86 in patients with NSCL/P(x2=8.27,df=1,P＜0.05).A1 allele frequency was 0.17 and A2 allele frequency was 0.83 in the bilateral cleft lip with or without cleft palate.A1 allele frequency was 0.13 and A2 allele frequency was 0.87 in the unilateral cleft lip with or without cleft palate(x2=0.36,df=1,P＞0.05).There was no statistically significant between the case with family history and the case without family history(x2=0.34,df=1,P＞0.05).Conclusions The above data demonstrate that there is evidence for the association of TGF-α polymorphism with development of NSCL/P in Chinese. Key words: Syndrome; Cleft lip; Oleft lip and palate; Nonsyndromic cleft lip with or without cleft palate; Transforming growth factor α

Allelic and genotypic associations of DRD2 Taq I A polymorphism with heroin dependence in Spanish subjects: a case control study

BackgroundConflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism.MethodsWe compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients (207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects (98 males and 47 females).ResultsThe A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls (P = 0.011, odds ratio = 5.48, 95% CI 1.26–23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls (24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07–2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender (odds ratio = 1.77, 95% CI 1.15–2.70).ConclusionOur results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males.

The association between type 2 diabetes mellitus and A1/A2 polymorphism of glycoprotein IIIa gene

Glycoprotein IIIa (GpIIIa) is a membrane receptor, found in various tissues, that has two alleles: A1 and A2. Signalling cascade of GpIIIa is modulated by enzymes called calpains, proteases that may also influence glucose metabolism. There is one small study that shows a high association of A1/A2 polymorphism with type 2 diabetes mellitus. In our research we planned to evaluate the association of A1/A2 polymorphism with type 2 diabetes in a population of patients with ST elevation acute myocardial infarction (STEMI). The study comprised 352 individuals. From the cohort of patients hospitalised for STEMI we chose 113 patients with diagnosed diabetes (diabetic group) and 118 patients with STEMI and normal glucose metabolism (non-diabetic group). The population group consisted of 121 persons. Genotyping was performed by the restriction fragments length polymorphism (RFLP) method. The frequency of alleles in all groups was in Hardy-Weinberg equilibrium. The percentage of A2 allele carriers was comparable among all groups : 20.4% (diabetic patients), 23.7% (nondiabetic) and 21.5% (control group) (p>0.05). There was no significant difference in frequency of A2 allele among the groups. We have not observed any association between GpIIIa polymorphism with either type 2 diabetes or STEMI.

TNFA2 and d2 alleles of the tumor necrosis factor alpha gene polymorphism are associated with onset/occurrence of idiopathic membranous nephropathy

Idiopathic membranous nephropathy (IMN) has a strong association with the major histocompatibility complex HLA B8DR3(17)DQ2 haplotype. The tumor necrosis factor (TNF)A gene is located within the major histocompatibility complex region on chromosome 6. We have studied the influence of two functional polymorphisms; the -308 (promoter region) and the TNFd microsatellites on initiation and/or progression of IMN. This was a case-control study comparing data from 100 Caucasians patients (67 male subjects; 67%) with IMN to 232 Caucasians local controls (171 male subjects; 74%). We have analyzed genotypes and alleles distributions and the role of these polymorphisms in disease progression towards end-stage renal failure or patient death. For -308 TNFA polymorphism, distribution of genotypes was significantly different between IMN and controls (chi(2)=16.25; P=0.0003): the A2 allele frequency was 28.0% in IMN vs 15.3% in controls (chi(2)=14.57; P=0.0001). For TNFd polymorphism, alleles distribution (from d1 to d7) was also significantly different between IMN and controls (chi(2)=56.74; P<0.0001) with both diminished d3 allele frequency (chi(2)=27.30; P<0.0001; Pc=0.001) and increased d2 allele frequency (chi(2)=29.95; P<0.0001; Pc=0.001) in IMN. We could not isolate any significant and independent influence of these different genotypes on IMN disease progression. The TNFA2 and TNFd2 alleles were strongly associated with occurrence/initiation of IMN and should be considered as susceptibility genes for this disease.

Role of CYP17 and CYP19 polymorphisms in idiopathic recurrent miscarriages among South Indian women

Recent reports suggest the relevance of gene polymorphisms in predicting reproductive outcome. The present study was aimed at investigating the relationship between the 5′ UTR polymorphism of CYP17, a tetranucleotide repeat and a trinucleotide deletion polymorphism in CYP19. A case–control-based study approach was used, which included 143 cases and 88 controls from the South Indian population. A PCR-sequencing based genotyping was used to ascertain the status of the individual. The A1, A2 allele frequencies of CYP17 among the cases were 72 and 28% while among the controls were 68 and 32% respectively (OR 1.21, 95% CI: 0.63–2.32). The 7/7 repeat of CYP19 was the predominant one with a distribution frequency of 55% in the cases and 58% in the controls. The deletion was observed in 39% of the cases and 36% of the controls (OR 1.14, 95% CI: 0.62–2.10). Minor genotypes when taken together represented at a higher frequency in cases than those in controls (13 against 2%, P-value: 0.006). No statistically significant association exists between the CYP17 and CYP19 trinucleotide deletion polymorphisms and the risk of idiopathic recurrent miscarriages among women from South India. However, larger repeat numbers of the tetra nucleotide (except the common 7/11 genotype) showed significant association at 95% level.

CTLA-4 A49G Polymorphism and Autoimmune Blood Diseases.

The cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is expressed on T lymphocytes, and inhibits the T cell responses. CTLA-4 A49G polymorphism was found to be associated with various autoimmune diseases in recent studies. In this study we evaluated the frequency of CTLA-4 A49G polymorphism in patients with autoimmune hemolytic anemia and autoimmune thrombocytopenia. One hundred and fifty healthy Turkish subjects, 46 patients with autoimmune hemolytic anemia (AIHA) and 62 patients with autoimmune trombocytopenic purpura (ITP) were included to our study. In healthy controls; genotype frequencies were 48% for AA, 47.3% for AG and 4.7% for GG. A-allele frequency was 71% and G allele frequency was 29%. Allele frequencies were similar to the other European countries. In AIHA group; 21 patients had AA (45.6%), 21 had AG (45.6%), and 4 had GG (8.8%) genotype. A allele frequency was 68.4%, and G allele frequency was 31.6% which are similar to healthy controls. In ITP group; 38 had AA (61.3.%), 21 had AG (33.9%), and 3 had GG (4.8%) genotype. A allele frequency was 78.4 %, and G allele frequency was 21.6%. We found no difference between ITP patients and controls for CTLA-4 A49G polymorphism. In subgroup analysis however, we found that all CLL patients with AIHA had CTLA-4 A49G polymorphism (3 had AG, 1 had GG). This may suggest that CTLA-4 A49G polymorphism is an important risk factor for the development of AIHA in CLL patients. Further genetic and clinical studies are required to understand the exact role of CTLA-4 A49G polymorphism in the development of autoimmune diseases.

A common A340T variant in PINK1 gene associated with late-onset Parkinson's disease in Chinese

Parkinson's disease (PD) is a complex neurodegenerative disease with genetic risk factors. Common variants in genes implicated in hereditary forms of parkinsonism may be predisposing factors for sporadic PD. Recent studies have demonstrated that mutations in PINK1 (PARK6 locus) gene, encoding PTEN-induced kinase 1, are associated with both familial recessive and sporadic early onset parkinsonism. In order to assess whether the coding variant A340T contributes to the risk of late-onset PD, we performed an association study of 539 PD patients with an onset age at or older than 50 and 525 controls in Chinese Han. Genotyping was performed by denaturing high performance liquid chromatography (DHPLC) combined with sequencing analyses. The A-allele frequency was 6.2% in PD and 4.2% in controls ( p = 0.0404), while G/A genotype frequencies were 12.4% in PD and 8.4% in the controls ( p = 0.0350). Our results yielded significant evidence for disease association between PINK1 A340T and PD with later onset (OR 1.55, 95% CI 1.04–2.32, p = 0.0393), thus suggesting that PINK1 A340T variant may contribute to the risk for late-onset PD in Chinese.

Association analysis between the dopamine D4 receptor gene and the 5-HT2A receptor gene and schizophrenia in Chinese

目的 探讨湖南地区汉族人群多巴胺D4受体(DRD4)基因和5-羟色胺2A(5-HT2A)受体基因与精神分裂症遗传易感性的关系及其相互作用对精神分裂症的影响.方法 81例精神分裂症患者单一用氯氮平治疗6～8周,利用阳性与阴性症状量表(PANSS)评定氯氮平的疗效,并根据量表的减分率将患者分为有效和无效两组.采用聚合酶链式反应(PCR)及限制性片段长度多态性(RFLP)技术检测患者组和对照组DRD4基因48 bp可变串联重复(VNTR)多态性及5-HT2A受体基因T102C多态性的基因型及等位基因的频率.结果 有效组患者DRD4*3/5基因型(DRD4*3/5)频率(40.3%)明显高于对照组(23.9%).DRD4*3等位基因携带者中,精神分裂症5-HT2A受体基因的A2等位基因频率(50.0%)显著高于对照组(30.0%);非DRD4*5/5携带者中,精神分裂症5-HT2A受体基因的A2/A2基因型(22.0%)及A2等位基因频率(48.8%)显著高于对照组(5.0%;32.5%).结论 DRD4基因48 bp VNTR多态性可能与精神分裂症的某些亚型(对氯氮平有效者)遗传易感性相关.DRD4基因和5-HT2A受体基因可能存在交互作用,DRD4 *非5/5基因型及携带DRD4 * 3等位基因者可能影响5-HT2A受体基因A2等位基因及A2/A2基因型与精神分裂症关系。

THE TAQI DRD2 A1 ALLELE IS ASSOCIATED WITH ALCOHOL-DEPENDENCE ALTHOUGH ITS EFFECT SIZE IS SMALL

Numerous studies of the relationship between the TaqIA DRD2 A1 allele and alcohol-dependence have been performed and many of these have shown an association whereas others have not (Noble, 2003). This has consequently generated some controversy as to whether such an association actually exists (Noble, 2003). In the two recent meta-analyses by Noble (2003) and Young et al. (2004) some very important methodological issues have been discussed, which need to be addressed in forthcoming studies. Thus, the sample size is of great importance. In case-control studies it has been estimated that to detect the role of genes with small effect size of approximately 2, which is in the range of the DRD2 A1 allele-alcoholism relationship, case-control sets of 300-400 subjects are necessary (Noble, 2003). In the present study, we have consequently recruited a large number of subjects, 375 alcohol-dependent individuals, who were treated as inpatients for alcohol withdrawal symptoms and out of these 357 could be evaluated. As controls, 578 individuals screened and 254 individuals unscreened for alcohol consumption were used. Thus, the total number of subjects was 1217. In the present study, in which the TaqI A1/A2 DRD2 polymorphism was in Hardy-Weinberg equilibrium in the patient group and the two control groups, we found that the TaqI DRD2 A1/A2 genotype frequency differed significantly between the alcohol-dependent group and both the total and screened control groups. Furthermore, the TaqI DRD2 A1 allele frequency was significantly overrepresented in the alcohol-dependent subjects as compared with both the total and screened control groups. The odds ratio for alcohol-dependency being associated with the A1 allele was 1.34. Consequently, the findings in this study lend further support to the notion of an association between the DRD2 A1 allele and alcohol-dependence, although the effect size of the DRD2 A1 allele is small.

Polymorphisms of DNA Repair Genes: ERCC1 G19007A and ERCC2/XPD C22541A in a Northeastern Chinese Population

DNA repair systems are responsible for maintaining the integrity of the genome and have a critical role in protecting against mutations that can lead to cancer. DNA repair gene products of ERCC1 and ERCC2/XPD are involved in the nucleotide excision repair pathway. The allele frequencies of the polymorphisms ERCC1 G19007A and ERCC2/XPD C22541A were examined in a northeastern Chinese population. The allele frequencies were 0.21 (A) and 0.79 (G) for ERCC1 G19007A and 0.49 (A) and 0.51 (C) for ERCC2/XPD C22541A. Comparison with average frequencies from previously reported Caucasian studies demonstrated that the A-allele frequency of ERCC1 G19007A was much lower in the northeastern Chinese population, indicating a remarkable ethnic difference (chi((1)) (2) = 160.09, p < 0.001), and that allele frequencies of ERCC2/XPD C22541A showed marginal racial differences (chi((1)) (2) = 4.36, p = 0.04). We have previously reported that both homozygote carriers of the A-allele as well as homozygous carriers of a high-risk haplotype (which includes the AA genotype in ERCC1 G19007A) were at increased risk of basal cell carcinoma, breast cancer, and lung cancer among Caucasians. The low A-allele frequency of ERCC1 G19007A in the Chinese population may suggest that the genetic contribution to cancer risk differs substantially between ethnic groups.

Risk of cerebral venous thrombosis and novel gene polymorphisms of the coagulation and fibrinolytic systems

Genetic thrombophilic conditions such as those associated with Factor V Leiden (FVL) and the prothrombin mutant (PT G20210A) have been identified as risk factors for cerebral venous thrombosis (CVT). Recently, a single nucleotide polymorphism (SNP) of the thrombin activatable fibrinolysis inhibitor (TAFI G-438A) has been shown to be associated with lower TAFI levels and to decrease the risk for peripheral venous thrombosis. Furthermore, a protective role in juvenile stroke was shown for a SNP of the vitamin K dependent protein Z (PZ Intron F G79A) which is linked with low PZ levels. In 77 consecutive patients with CVT and in 203 randomly selected population controls from the same region of Southern Germany, we investigated the following functional SNPs using PCR and restriction fragment analysis techniques: TAFI G-438A, PZ Intron F G79A, FVL and PT G20210A. The prevalence of FVL tended to be higher (OR 2.08, 95 % CI 0.91-4.75, p = 0.06) and that of PT G20210A (OR 4.57, 95 % CI 1.45-14.44, p = 0.007) was significantly higher in patients with CVT than in controls. The A-allele frequency of the TAFI G-438A polymorphism did not significantly differ between patients (21.3 %) and controls (26.9%; OR 0.71, 95 % CI 0.45-1.12; p = 0.17). For the PZ G79A SNP, the frequency of the A-allele was 19.5% in CVT and 24.6% in controls (OR 0.77, 95 % CI 0.49-1.21; p = 0.31). In this large series of CVT patients, a positive association with established thrombophilic risk factors FVL and especially the PT G20210A mutation was confirmed. In contrast, our study found no significant association of CVT with SNPs of the TAFI and the PZ genes. Other than testing for FVL and the PT G20210A mutation, exploration of these potential thrombophilic variants seems to be of limited value in the investigation of CVT.

Stromelysin‐1 promoter 5A/6A polymorphism is an independent genetic prognostic risk factor and interacts with smoking cessation after index premature myocardial infarction

To evaluate the prognostic roles of multiple polymorphisms and smoking cessation for premature myocardial infarction (MI). We studied 170 patients with MI onset before the age of 45 years (range 27-45 years, 84% men) and analyzed the traditional risk factors and several candidate genes' associations with their subsequent coronary events. Follow-up data were available for a total of 162 individuals (95.3%) with the other 38 individuals (4.7%) being lost-to-follow-up premature MI patients. During a mean period of 4.43 years' follow-up, diabetes mellitus (DM), hypertension, hypercholesterolemia and Killip's status > or =II were more frequent among patients with subsequent cardiac events (all P-values <0.05). The frequency of 5A allele of stromelysin-1 gene was significantly higher among event group (P = 0.01). Smoking cessation after MI, use of beta-blocker or angiotensin-converting enzyme inhibitor (ACEI) could improve outcome (all P-values <0.05). After multivariate analysis, we found that DM was an independent risk factor for survival [Hazard ratio (HR) 2.45, P = 0.01]. Successful smoking cessation and therapy with ACEI could have a protective effect (HR 0.33 and 0.09, P = 0.01 and <0.01, respectively). The stromelysin-1 5A gene polymorphism was also an independent survival predictor (HR 2.51, P = 0.03). In addition, smoking cessation could significantly modify the risk, especially among patients with 5A allele polymorphism (HR 6.75 vs. 1.50). We thus conclude that the stromelysin-1 gene polymorphism alone or in combination with smoking cessation can influence the prognosis after index premature MI.

Polymorphisms in the DBH and DRD2 gene regions and smoking behavior

The DRD2 TaqI A and DBH-1021 C/T polymorphisms were genotyped in smoking alcoholics (N = 100), non-alcoholic smokers (N = 120) and nonsmoking controls (N = 112). Alcoholic and non-alcoholic smokers presented a higher frequency of the DRD2 TaqI A1 allele (P = 0.04) than non-smoking controls. Individuals who had at least one DBH-1021 T allele smoked fewer cigarettes per day than CC homozygotes (P = 0.03). These results are coherent with the expected effects of these polymorphisms on dopaminergic function.

The Association Between the DRD2 TaqI A Polymorphism and Smoking Cessation in Response to Acupuncture in Koreans

The response to acupuncture is presumed to differ with the individual; this variation might be due to genetic differences. Therefore, we examined whether the DRD2 TaqI A polymorphism is associated with the response to acupuncture in the treatment of smoking cessation in a Korean population. A total of 231 healthy Korean male smokers participated in this study. The subjects underwent three manual auricular acupuncture treatments in one week. After 1 week, high and low responders to the acupuncture treatment were selected according to their cigarette consumption and the desire to smoke. A DRD2 TaqI A restriction enzyme fragment length polymorphism (RFLP) study examined genomic DNA extracted from blood samples. The proportions of high, intermediate, and low responders were 28.6, 55.4, and 16.0%, respectively. The RFLP study showed that the distribution of the DRD2*A genotype and allele frequencies differed significantly between the high and low responders (chi(2) test, p = 0.031 and 0.016, respectively), and that high responders had a higher DRD2*A2 allele frequency than low responders. Our findings suggest that DRD2 TaqI A polymorphism is related to acupuncture response in smoking cessation treatment.