Fcgamma receptor IIIA polymorphism as a risk factor for acute poliomyelitis

Poliomyelitis is a viral infection that causes flaccid paralysis in approximately 1% of cases. The Fc receptors for immunoglobulin G (FcgammaR) are associated with modifying effects of several infectious and autoimmune diseases. To assess the influence of FcgammaR polymorphisms on the acute and late course of poliomyelitis, 110 Norwegian patients with well-defined histories of acute poliomyelitis were genotyped, of whom 50 suffered from the postpolio syndrome (PPS). In comparison with healthy control subjects without a history of poliomyelitis, significantly fewer patients had the FcgammaRIIIA genotype V/V (P<.01). However, this genotype was not an independent risk factor for PPS. The FcgammaRIIA and IIIB genotypes and allele frequencies did not differ between the patients and control subjects. The FcgammaRIIIA V/V genotype may lower the risk for contracting acute poliomyelitis through better clearance of poliovirus.     

The Fcgamma receptor IIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians but not non-Caucasians

OBJECTIVE: To determine whether inheritance of Fcgamma receptor (FcgammaR) alleles conferring lower affinity for IgG binding increases the risk of developing lupus nephritis. METHODS: We compared the frequency of low-affinity alleles of two FcgammaR polymorphisms (FcgammaRIIA and FcgammaRIIIA) among 235 patients with systemic lupus erythematosus (SLE) and proven nephritis (nephritis patients) and among 352 SLE patients with no evidence of renal disease (non-nephritis control subjects). The ethnic distribution of patients in the study was 49% Caucasian, 20% Hispanic, 17% Asian/Pacific Islander, 12% African American, and 2% from other ethnic groups. All patients were genotyped for the FcgammaRIIA-131R/H and FcgammaRIIIA-158V/F polymorphisms. We used contingency table analysis to compare allele and genotype distributions for nephritis patients and nonnephritis control subjects, including ethnic-specific strata. Multivariate logistic regression analyses included sex and disease duration as covariates. RESULTS: Univariate and multivariate analyses demonstrated a striking association between the low-affinity FcgammaRIIIA-158F allele and FF genotype and the risk of nephritis among Caucasians, but not among non-Caucasians (multivariate odds ratio [OR] 2.6 for Caucasians with FF genotype), (P = 0.0017). This association was even stronger among Caucasians with severe nephritis (OR 4.4, P < 0.0001). In contrast, inheritance of the low-affinity FcgammaRIIA-131R allele (and RR genotype) was not associated with an increased risk of lupus nephritis among any of the ethnic groups examined. CONCLUSION: The FcgammaRIIIA-158F allele is a major risk factor for the development of lupus nephritis among Caucasians, but not among non-Caucasians. These results suggest that ethnic variation is critical in defining the specific genetic factors underlying the pathogenesis of SLE, and they have important prognostic and therapeutic implications as well.     

Interleukin-1 gene cluster polymorphisms and risk of coronary artery disease

BACKGROUND AND OBJECTIVES: The pro-inflammatory cytokine interleukin (IL)-1 has been suggested to play a role in atherosclerosis. Several genetic polymorphisms have been described in the genes of the IL-1 cluster and associations with coronary artery disease (CAD) have been reported, although with contrasting results. DESIGN AND METHODS: The associations of a variable number tandem repeat (86 bp) polymorphism in intron 2 of interleukin-1 receptor antagonist (IL1-RA) and of the 511 C/T polymorphism of IL-1b with the risk of CAD were studied. Three hundred and thirty-five case (CAD+) patients with angiographically documented CAD (stenosis >50% in at least one major coronary artery) were compared with 205 unrelated individuals free of CAD signs at angiogram (CAD- controls). One hundred and two (30.5%) CAD+ patients had single-vessel disease (SVD) and 233 (69.5%) multiple-vessel disease (MVD). RESULTS: There was no statistically significant difference in either genotype distribution or allele frequency of both IL-1 RA and IL-1b 511 C/T polymorphisms between CAD+ cases and CAD- controls. Moreover in multivariate analysis, adjusting for multiple comparisons and confounding factors, no difference was found in IL-1 RA genotype distribution between patients with SVD or MVD. INTERPRETATION AND CONCLUSIONS: Our study does not support the association between IL-1 RA intron 2 VNTR and IL-1b 511 C/T polymorphisms and the risk of CAD in individuals undergoing coronary angiography.     

Homozygosity for angiotensinogen 235T variant increases the risk of myocardial infarction in patients with multi-vessel coronary artery disease

OBJECTIVE: Molecular variants of the angiotensinogen (AGT) and the angiotensin II type 1 receptor (ATR) genes have been associated with the risk of coronary artery disease (CAD) and myocardial infarction (MI), but data so far available are conflicting. The primary object of the paper is to verify this possible association by a rigorous, angiographically controlled study in a large sample of patients with or without multi-vessel CAD. DESIGN: We designed a large case-control study in Italian patients candidates for coronary artery bypass grafting, with angiographically documented multi-vessel CAD, compared to subjects with angiographically documented normal coronary arteries. METHODS AND RESULTS: AGT M235T and ATR A1166C gene polymorphisms were analysed in 699 subjects; 454 patients were candidates for coronary artery bypass grafting, having angiographically documented (mainly multi-vessel) CAD. An appropriate documentation of previous MI was obtained from 404/454 (89%, 247 with and 157 without MI). Subjects (n = 245) with angiographically documented normal coronary arteries, were included as control group (CAD-free group). CAD patients had a substantial burden of conventional risk factors as compared with controls free of coronary atherosclerosis. Age, gender, smoking habit and number of stenosed vessels were the only differences between patients with or without previous myocardial infarction, who were similarly exposed to the other conventional risk factors (including hypertension). AGT M235T and ATR A1166C allele and genotype frequencies were similar between CAD and CAD-free patients. In the CAD group, AGT 235T allele was found more frequently in subjects with a previous myocardial infarction (0.494 versus 0.414; P < or = 0.05). By logistic regression, homozygosity for AGT 235T variant appeared to confer 1.9-fold increased risk for MI in both the univariate and the multivariate (adjusted for age, gender, smoking habit and number of stenosed vessels) model. CONCLUSIONS: AGT 235 T homozygous patients with multivessel CAD have an increased risk of myocardial infarction as compared with subjects with clinically similar phenotype but different genotype.     

Lack of evidence for association between endothelial nitric oxide synthase gene polymorphisms and coronary artery disease in the Australian Caucasian population

BACKGROUND: Genetic polymorphism in the gene for endothelial nitric oxide synthase (eNOS) has been identified as a potential risk factor for the development of premature coronary artery disease (CAD). We determined whether the eNOS 4ab, G894T, and T-786C polymorphisms are associated with premature coronary artery disease. DESIGN: A case-control study. METHODS: PCR-based assays were used to compare the frequency of eNOS gene polymorphisms in 573 Caucasian subjects aged under 50 years presenting with symptomatic CAD and documented by coronary angiography, with or without myocardial infarction, to that of 624 similarly aged community controls without a history of symptomatic CAD. RESULTS: We found no difference in the frequency of 4ab genotypes between cases and controls: in the CAD subjects, the 4aa, 4ab, and 4bb genotype frequencies were 1.9%, 24.3% and 73.8% respectively, compared to 2.2%, 25.5% and 72.3% respectively for the controls. There was also no significant difference between cases and controls in the frequency of any allele (4a/4b, 894G/894T, -786C/-786T), or genotype for any of the polymorphisms. Similarly, logistic regression analysis showed no evidence for an association of the polymorphisms with premature CAD or myocardial infarction or any indication of an interaction between the polymorphisms and other CAD risk factors, including smoking. CONCLUSIONS: In a large case-control study, and in contrast to some earlier positive findings by others, we have found no evidence for an association between several eNOS gene polymorphisms and premature CAD in an Australian Caucasian population.     

Gene Polymorphisms for PAI-1 Are Associated with the Angiographic Extent of Coronary Artery Disease

Localized regulation of fibrinolytic protein gene expression is associated with the histologic extent of atherosclerosis. This regulation may be dependent on the presence of certain fibrinolytic protein gene polymorphisms. The relationship between the plasminogen activator inhibitor (PAI)-1 HindIII and the tissue plasminogen activator (t-PA) EcoR1 gene polymorphisms and the extent of coronary artery disease (CAD) were investigated in 49 Caucasian patients with symptomatic CAD. There was a strong association between PAI-1, but not t-PA, gene polymorphisms and the extent of CAD detected by coronary angiography. Patients homozygous for the presence or absence of the PAI-1 HindIII (1/1, 2/2 PAI-1) gene polymorphisms had a significantly greater extent of CAD (number of diseased vessels) than patients with the respective heterozygous forms (vs. 1/2 PAI-1, P = 0.05). Stepwise ordinal multiple regression analysis of classic CAD risk factors and fibrinolytic protein genotypes indicated that only the PAI-1 genotypes were predictive of the extent of angiographic CAD (P = 0.019). Analysis of variance between classic risk factors and fibrinolytic protein genotypes identified an association between t-PA genotypes and a history of prior infarction or stroke. Fibrinolytic gene polymorphisms for PAI-1 are associated with the extent of CAD in symptomatic patients and with certain risk factors for coronary atherosclerosis.     

FcgammaRIIIA-158V and rheumatoid arthritis: a confirmation study

OBJECTIVES: To develop a robust assay for genotyping the FcgammaRIIIA-158V/F polymorphism and to confirm the putative association between the FcgammaRIIIA-158V allele and rheumatoid arthritis (RA). METHODS: This allelic association study examined the FcgammaRIIIA-158V/F polymorphism for association with RA. A novel single-stranded conformational polymorphism assay was used to genotype 828 RA patients and 581 controls from the UK. RESULTS: The FcgammaRIIIA-158V allele was associated with both RA (P=0.02) and nodules (P=0.04). Individuals homozygous for this higher affinity allele had a significantly increased risk of RA (OR 1.53, 95% CI 1.08-2.18) and the development of nodules (OR 2.20, 95% CI 1.20-4.01). There was no evidence of an interaction with the shared epitope. CONCLUSIONS: We have developed a novel assay to genotype the FcgammaRIIIA-158F/V polymorphism and confirmed that homozygosity for the FcgammaRIIIA-158V allele is associated with UK Caucasian RA, particularly in those individuals with nodules, suggesting FcgammaRIIIA may play a role in determining disease severity or in the development of nodules per se.     

Gene polymorphisms in patients below 35 years of age who underwent coronary artery bypass surgery

OBJECTIVE: Genetic bases for novel prothrombotic, inflammatory risk factors may play a role in the early onset of coronary artery disease. METHODS: Twenty-one patients below 35 years of age who underwent coronary bypass grafting between 2002 and 2004 constituted the study group and were compared with 50 healthy, age and sex-matched controls. Gene analysis for genetic polymorphisms of angiotensin-converting enzyme, prothrombin G20210A, tumour necrosis factor-alpha G308A, factor V Leiden and interleukin-6 genes was carried out. RESULTS: The control group was 98% homozygous for the factor V Leiden GG allele and 2% heterozygous for the GA allele. On the other hand, the study group was 76.2% homozygous for the GG allele, and 23.8% heterozygous for the GA allele (P<0.05). Homozygosity for factor V Leiden mutation (AA) was not encountered in either group. With regard to interleukin-6, 70.0% of the control group demonstrated homozygosity for the GG allele and 30.0% showed heterozygosity (GC). The study group was 52.4% homozygous for the GG allele and heterogenicity was similar in this group (28.6% GC). On the other hand, 19.0% of this group demonstrated CC homogenicity (P<0.05). No difference was observed with regard to gene polymorphisms. CONCLUSIONS: Gene polymorphisms with regard to prothrombotic factor V Leiden mutation and inflammatory marker interleukin-6 may play a role in the pathogenesis of early-onset coronary artery stenosis in patients below 35 years of age.     

Variant genotypes of FcgammaRIIIA influence the development of Kaposi's sarcoma in HIV-infected men

Disturbances in inflammatory cytokine production and immune regulation coupled with human herpesvirus-8 (HHV-8) infection underlie the current understanding of the pathogenesis of Kaposi's sarcoma (KS), the most common HIV-associated malignancy. The low affinity Fc gamma receptors (FcgammaR) for IgG link humoral and cellular immunity by mediating interaction between antibodies and effector cells, such as phagocytes and natural killer cells. We examined the frequency of polymorphic forms of the low affinity FcgammaRs, FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB in 2 cohorts of HIV-infected men with KS and found that the FcgammaRIIIA genotype exerts a significant influence on susceptibility to or protection from KS. The FF genotype was underrepresented in patients with KS, whereas the VF genotype was associated with development of KS. A similar association was observed between FcgammaRIIIA genotypes and HHV-8 seropositivity. These observations suggest a possible role for FcgammaRIIIA in the development of KS during HIV infection.     

The D allele of the angiotensin-converting enzyme gene contributes towards blood LDL-cholesterol levels and the presence of hypertension.

Coronary artery disease is a polygenic disease whose phenotypic manifestation depends on the interaction of the genetic background with a number of environmental factors. Recently, the gene coding for the angiotensin-converting enzyme (ACE) has been characterized and a deletion/insertion (D/I) polymorphism was defined. The prevalence of the three genotypes and their association with coronary artery disease (CAD) differ in different population groups. Mostly, the D allele was found as a significant risk factor for CAD, independently from other risk factors. In the present study, we determined the distribution of ACE alleles (D or I) in a cohort of healthy Israeli men and examined the correlation of the different genotypes with various CAD risk factors. We found LDL cholesterol levels to be highest in the DD genotype group, intermediate in the DI genotype group and lowest in the II genotype group. We also found higher blood pressure levels in subjects bearing the D allele compared to II homozygous subjects. In conclusion, it appears that the genetic influence of the D/I polymorphism on CAD manifests primarily through traditional risk factors.     

Immunoglobulin G fc-receptor (FcgammaR) IIA,IIIA, and IIIB polymorphisms related to disease severity in rheumatoid arthritis

OBJECTIVE: Fc receptors for IgG (FcyR) modulate immune responses. FcyR are expressed on various leukocytes and contain allelic polymorphisms with different capacity for IgG binding and phagocytosis. We investigated the distribution of FcgammaRIIA, FcgammaRIIIA, and FcgammaRIIIB polymorphisms in rheumatoid arthritis (RA) and whether they were related to disease expression and severity. METHODS: Ninety-six controls and 114 patients fulfilling American College of Rheumatology (ACR) criteria for RA were genotyped for FcgammaRIIA, IIIA, and IIIB using polymerase chain reaction. Physician's global assessment of RA type estimated RA disease expression. In addition, usual measures of disease activity were recorded. RESULTS: The genotype and allele frequencies did not differ significantly between the RA patients and the controls. Patients homo or heterozygous for the FcgammaRIIA arginine (R) allele had significantly more aggressive RA and swollen joints than patients homozygous for the FcgammaRIIA histidine (H) allele. Although there was a tendency of more severe disease among patients homo or heterozygous for the FcgammaRIIIA valine allele, there were no significant findings with the disease activity for the FcgammaRIIIA and FcgammaRIIIB genotypes. CONCLUSION: FcgammaRIIA is implicated as a possible disease modifying gene in RA. Individuals homozygous for the FcgammaRIIA R allele have less efficient binding of IgG2 subclasses than individuals homozygous for the H allele. Less effective processing of circulating immune complexes in RA patients homozygous for the FcgammaRIIA R allele may therefore contribute to a more unfavorable course.     

The Association between Myeloperoxidase-463G/A Gene Polymorphism and Coronary Artery Disease

Objectives To study the relationship between myeloperoxidase （MPO）-463G/A polymorphisms and susceptibility to coronary artery disease （CAD） in Han people of north Anhui province. Methods The case group consisted of 79 patients who had all angiographically proven CAD were retrospectively studied. Used polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） methods to decide the genotype of all the patients. Results The frequency of AA homozygotic type in Han people of Anhui province was 1.4%. The risk of CAD for person carrying at least one A allele genotype （ GA and AA） was 0. 37 times of GG genotype. The severity of coronary artery stenosis in CAD patients carrying at least one A allele genotype was 0. 197 times of GG genotype （ P 〈 0. 05 ）. Conclusions The frequency of AA homozygotic type and MPO-463G/A polymorphism in Han people of Anhui province influenced the risk of CAD. A allele had protective function in CAD.     

基质金属蛋白酶-3基因单核苷酸多态性与冠状动脉粥样硬化程度的关联研究

目的 探讨MMP-3基因单核苷酸多态性(SNP)与冠心病患者冠状动脉粥样硬化程度间的相关性.方法 入选经冠状动脉造影证实的汉族冠心病患者1371例及健康对照695例,选择MMP-3-1612 5A/6A、-376C/G、Glu45Lys等SNPs位点,采用聚合酶链式反应-限制性内切酶片段长度多态性(PCR-RFLP)方法确定基因型.X2检验用于单因素分析时检验SNP位点与冠状动脉粥样硬化程度间的关联.结果 (1)-1612 5A/6A多态性位点在冠心病患者单支病变、双支病变、三支病变组中5A等位基因频率分别是0.185,0.183,0.152;-376C/G多态性位点在以上三组中-376G等位基因频率分别是0.329,0.326,0.325;Glu45Lys多态性位点在以上三组中45Lys等位基因频率分别是0.423,0.417,0.405.(2)-1612 5A/6A多态性位点5A等位基因频率在三支病变组中明显低于单支病变组(OR=0.74,P=0.04);相对于6A/6A基因型,含有5A等位基因的纯合子及杂合子频率在三支病变组明显低于单支病变组(OR=0.74,P=0.04).结论 中国汉族冠心病患者中MMP-3基因-1612 5A/6A多态性位点可能与冠心病患者冠状动脉粥样硬化程度相关,5A等位基因可能对冠状动脉粥样硬化的进展有保护作用.     

Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease

OBJECTIVES: Our hypothesis was that functional polymorphisms in matrix metalloproteinase (MMP) genes may act as susceptibility factors for the development of coronary aneurysms (CAs). BACKGROUND: Different forms of remodeling have been described at the level of coronary arteries; CA, reported in 1% to 5% of patients with angiographic evidence of coronary artery disease (CAD), are one of them. Matrix metalloproteinases have been implicated in the pathogenesis of aneurysm development through increased proteolysis of extracellular matrix proteins. METHODS: We screened 3,862 patients who underwent coronary angiography and identified 113 patients with CAD with at least one CA (CA group); these patients were matched with 226 patients with CAD without CA (control group). The -1,306 C/T MMP-2, 5A/6A MMP-3, CA-repeat MMP-9 and -82 A/G MMP-12 polymorphisms were determined. RESULTS: The MMP-2, MMP-9 and MMP-12 polymorphisms were not associated with CA. By contrast, the 5A/5A genotype of MMP-3 was significantly more frequent in the CA group than in the control group (31% vs. 18%, p = 0.015); similarly, the MMP-3 5A allele was more frequent in the CA group (p = 0.009). Three variables were independently associated with CA: the MMP-3 5A/5A genotype (odds ratio [OR] = 2.23, 95% confidence interval [CI] [1.27 to 3.93]), a previous myocardial infarction (OR = 1.91, 95% CI [1.14 to 3.20]) and a history of aortic aneurysm (OR = 21.06, 95% CI [2.35 to 188]). CONCLUSIONS: The MMP-3 5A allele is associated with the occurrence of CA. Our results suggest that an increased proteolysis in the arterial wall may act as a susceptibility factor for the development of CA in patients with coronary atherosclerosis.     

Glutathione peroxidase 1 genotype is associated with an increased risk of coronary artery disease

OBJECTIVE: Oxidative stress is implicated in the pathogenesis of many human diseases including atherosclerosis. Human glutathione peroxidase 1 (hgpx1) participates in limiting cellular damage caused by oxidation. A characteristic polyalanine sequence polymorphism in exon 1 of hgpx1 produces three alleles with five, six or seven alanine (ALA) repeats in this sequence. The objective of this study was to determine whether hgpx1 genotype is associated with an altered risk of coronary artery disease (CAD). METHODS: The frequency of the ALA6 allele was determined in 207 men with angiographic evidence of significant CAD compared to a control group (n = 146), by analysing the lengths of polymerase chain reaction fragments containing the ALA repeat polymorphism. Additional information was collected on severity of CAD, presence or absence of a prior acute myocardial infarction (AMI), smoking status, body mass index (BMI) and other clinical data. RESULTS: There was a significant association between individuals with at least one ALA6 allele and an increased risk of CAD after adjustment for age, BMI and smoking status (odds ratio, 2.07, 95% confidence interval, 1.08-3.99, P = 0.029). However, there was no association between hgpx1 genotype and a previous history of AMI or hgpx1 genotype and severity of CAD. CONCLUSION: We conclude that individuals possessing one or two ALA6 alleles appear to be at a modest increased risk of CAD. This observation merits further investigation in other patient populations.     

Lack of Association of Angiotensin Converting Enzyme Gene Polymorphism or Serum Enzyme Activity With Coronary Artery Disease in Japanese Subjects

The association of an insertion/deletion (I/D) polymorphism in the angiotensin converting enzyme (ACE) gene or the serum activity of ACE with coronary artery disease (CAD) was investigated in Japanese men and women. The ACE genotype of 947 CAD subjects who underwent coronary angiography and of 893 control subjects was determined by polymerase chain reaction analysis. No association of the DD genotype or the D allele with CAD was observed in men or women. In a low risk group (defined by a body mass index below the median value and the absence of a history of hypertension, diabetes mellitus, and hypercholesterolemia), there was also no association between the ACE gene polymorphism and CAD. No significant difference in serum ACE activity was detected between CAD subjects and controls of all genotypes or of the same genotype, whereas a significant association was apparent between serum ACE activity and ACE genotype for both CAD subjects and controls among both men and women. These results indicate that the ACE I/D polymorphism and genotype associated variation in serum ACE activity are not risk factors for CAD in Japanese men or women.     

PON1 M/L55 mutation protects high-risk patients against coronary artery disease

The paraoxonase (PON) gene family contains at least three members: PON1, PON2, and PON3. The enzyme PON1 has been implicated in the pathogenesis of atherosclerosis. Recently, an association between PON2 and quantitative metabolic phenotypes, such as plasma lipoproteins, plasma glucose, and coronary artery disease (CAD), has been reported. We analyzed two common polymorphisms in PON1 (i.e., M/L55 and R/Q 192 mutations) and PON2 (i.e., G/A148 and C/S311 mutations) in 352 high-risk patients with angiographically defined CAD. These results were compared to those in 380 age- and sex-matched control subjects at high risk for CAD. Polymerase chain reaction with specific primers followed by Hsp92, Alw1, DdeI and Fnu4HI restriction digestion were employed to identify the PON1 M/L55 and R/Q192 and the PON2 G/A148 and C/S311 genotypes, respectively. Univariate analysis showed a higher prevalence of the MM genotype (12% vs. 5%; p=0.004) for the PON1 M/L55 polymorphism and the GG genotype (21% vs. 15%; p=0.047) PON2 G/A148 polymorphism in the control subjects. The PON1 M/L55 mutation (MM genotype) was associated with lower triglyceride levels and the PON2 G/A148 mutation (GG genotype), with higher total and low-density lipoprotein (LDL)-cholesterol levels. No mutation was associated with the number of major coronary artery vessels with a >50% reduction in lumen diameter. Multiple regression analysis disclosed smoking, a family history of CAD, high-density lipoprotein (HDL)-cholesterol and the PON1 M/L55 mutation [OR=0.59 (CI95%: 0.42-0.82); p=0.002] as independent markers for CAD. In contrast to traditional coronary risk factors, the PON1 M/L mutation can be considered predictive of protection against CAD.     

Association between the Ser128Arg variant of the E-selectin and risk of coronary artery disease in the central China

BACKGROUND: The E-selectin mediates the interaction of activated endothelial cells with leukocytes and plays a fundamental role in the pathogenesis of coronary atherosclerosis. It has been suggested that a S/R (Ser128Arg) polymorphism of E-selectin might be associated with the predisposition to coronary artery disease (CAD). Our purpose was to determine whether this S/R polymorphism influences the risk of CAD in Chinese patients. METHODS AND RESULTS: We studied the human E-selectin gene polymorphism in a Chinese population by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). This polymorphism was determined in 248 CAD patients and in 256 control subjects. Frequencies of the SS, SR, and RR genotypes were found as 86.7%, 13.3%, and 0.0% in CAD patients and 93.8%, 6.2%, and 0.0% in control subjects, respectively. Frequency of the R allele was higher among CAD patients compared to controls(6.7% vs. 3.1%). However, either the genotype or the allele distribution of Ser128Arg polymorphism of E-selectin was statistically significantly different between the two groups (P<0.05). The odds ratio for the risk of CAD associated with the R allele was 2.21 (CI95%:1.20-4.07). CONCLUSIONS: These results suggest that the SR genotype of the E-selectin gene polymorphism in codon 128 is a genetic factor that may determine an individual's susceptibility for CAD in Chinese.     

The prothrombin 20210A allele and the factor V Leiden are associated with venous thrombosis but not with early coronary artery disease.

This study was performed in order to establish the role of the prothrombin 20210 G/A and factor V Leiden (R506Q) polymorphisms in the susceptibility to develop venous thromboembolism and early coronary artery disease (CAD). These polymorphisms were determined in 82 consecutive patients with venous thromboembolism, 175 male patients with early CAD, and 200 healthy controls from the same Caucasian population (Asturias, Northern Spain). DNA was amplified using polymerase chain reactions and digested with the appropriate restriction enzymes in order to define the prothrombin and factor V genotypes. The prevalence of the heterozygous for the prothrombin A allele was 3.5% in the general population and 15.8% in patients with venous thrombosis (P = 0.0007); the frequency was 4% in patients with early CAD. No sex-related differences in the prevalence of the A allele were observed, and the average age at the first venous thromboembolic event was similar between GG and AG patients. The frequency of carriers of the factor V Leiden polymorphism was 9.75% among patients with venous thromboembolism, compared with 3.5% among controls, and 3.4% in the patients with CAD. Our data showed an association between venous thromboembolism and the AG genotype at the prothrombin 20210 G/A polymorphism. This polymorphism was not related to an increased risk for early CAD in our population of male patients.     

Low-binding alleles of Fcgamma receptor types IIA and IIIA are inherited independently and are associated with systemic lupus erythematosus in Hispanic patients

OBJECTIVE: To examine the relationship between allelic polymorphisms of IgG receptors (FcgammaR) and the development of lupus nephritis in a prospective study, and to determine the distribution of FcgammaR haplotypes (FcgammaRIIA and FcgammaRIIIA genotypes) in lupus patients and disease-free control subjects. METHODS: We studied 67 Hispanic systemic lupus erythematosus (SLE) patients from a prospective study of outcome and 53 disease-free control subjects. Patients were followed up longitudinally for 3 years. FcgammaRIIA and FcgammaRIIIA genotypes were determined using allele-specific polymerase chain reaction. RESULTS: Nephritis was present in 28% of patients at entry into the study and in 69% at the end of 3 years. In the nephritis group (n = 46), as well as the entire SLE cohort, there was a predominance of genotypes with low-binding alleles (FcgammaRIIa-R131 and FcgammaRIIIa-F176) at both loci (SLE nephritis patients 89% versus controls 62%; P < 0.002; odds ratio 0.20 [95% confidence interval 0.05-0.6] for risk of nephritis in individuals homozygous for either FcgammaRIIa-H131 or FcgammaRIIIaV176). The frequency of individuals homozygous for high-binding alleles at either locus decreased as the burden of disease increased (P < 0.002, by Mann-Whitney test). There was no linkage disequilibrium between FcgammaRIIA and FcgammaRIIIA in Hispanics, yet in the SLE patients, there was a clear overrepresentation of the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype (SLE patients 48% versus controls 30%) and a decrease in the frequency of the high-binding haplotype (4% versus 23%) (P < 0.002). CONCLUSION: We observed an increase in the frequency of low-binding FcgammaR alleles in an SLE population with a high prevalence of renal disease. The apparent selection for the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype in Hispanic patients suggests that low-binding alleles of both FcgammaRIIa and FcgammaRIIIa confer risk for SLE and may act additively in the pathogenesis of disease, whereas the high-binding haplotype FcgammaRIIa-H131;FcgammaRIIIa-V176 is protective, particularly in the homozygous state.