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PubMed2000

Angiotensin-converting enzyme gene polymorphism as a cardiovascular risk factor in children.

A family history of cardiovascular disease predicts cardiovascular risk in the next generation, which is either the result of inherited traits or certain living habits in some families. The aim of our study was to evaluate both variables and particularly the role of one of the possible genetic risk factors--angiotensin-converting enzyme (ACE) gene polymorphism. History and anthropometric and biochemical parameters, ACE gene polymorphism and carotid wall thickness--intima media thickness (IMT) were studied in two groups of children: in children whose parents had a stroke before the age of 45 years and in children without a positive family history. The preliminary results of the present study failed to confirm our hypothesis that ACE gene polymorphism is a cardiovascular risk factor in children of parents with premature stroke.

Adolescent↗
PubMed1995

Gene polymorphism but not catalytic activity of angiotensin I-converting enzyme is associated with coronary artery disease and myocardial infarction in low-risk patients.

BACKGROUND: An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been postulated to be associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). METHODS AND RESULTS: In the present study, the effects of I/D gene polymorphism and of ACE activity on CAD and MI were investigated in 920 individuals who underwent coronary angiography for diagnostic purposes. In the total population and in all CAD and MI groups, a strong association was observed between the gene polymorphism and ACE activities; DD genotypes had approximately twofold higher ACE activities than II genotypes. Although classic risk and protective factors of CAD and MI were identified, associations of ACE genotype and of ACE activity to CAD and MI were not detected in the total population. Among subjects defined to be at lower risk of MI by low body mass index and low cigarette consumption, however, an association of the DD genotype with MI was found. Exclusion of individuals with triglyceride levels > 140 mg/dL and cholesterol levels > 180 mg/dL revealed an association of the DD genotype with CAD. An association of the ACE activity with CAD or MI could not be demonstrated in any of the low-risk populations. CONCLUSIONS: Increased ACE activity obviously is not a risk factor of CAD or MI. The importance of the deletion polymorphism for the development of CAD and MI may be restricted to individuals without classic risk factors.

Case-Control Studies↗
PubMed2001

Effects of interleukin-1 gene polymorphisms on the development of coronary artery disease associated with Chlamydia pneumoniae infection.

OBJECTIVES: This study was done to elucidate the effects of interleukin (IL)-1 gene polymorphisms on coronary artery disease (CAD) associated with Chlamydia pneumoniae (CP) infection. BACKGROUND: It was suggested that CP was associated with CAD. However, genetic factors involved in CAD associated with CP infection are unknown. METHODS: We evaluated CP immunoglobulin G (IgG) seropositivity and IL-1 beta (a C/T transition at -511) and IL-1 receptor antagonist (IL-1Ra) (a variable-number repeat in intron 2) gene polymorphisms in 292 patients undergoing coronary angiography. RESULTS: Seropositivity for CP was present in 61% of patients with CAD versus 51% without CAD (p = NS). The percentage of patients having IL-1 beta (-511) C/C genotype and/or IL-1Ra (intron 2) 2- or 3-repeat allele was higher in patients with CAD than without CAD (29 vs. 16%, p < 0.025). To clarify the effects of these CAD-associated variants (IL-1 beta C/C and/or IL-1Ra 2- or 3-repeat), patients were divided into four groups. A stepwise increase in CAD prevalence was observed depending on CP seropositivity and the variants. Odds ratios (ORs) for CAD were 1.4 in the group with seropositivity alone, 1.7 with the variants alone and 3.8 with seropositivity and the variants. Such variants were associated with CAD in both patients with and without seropositivity. Interestingly, high prevalence of myocardial infarction (MI) was confined to the group with seropositivity and the variants (OR, 2.8). The variants were associated with MI only in patients with CP seropositivity. CONCLUSIONS: The IL-1 gene polymorphisms were found to play a role in the development of CAD, especially MI, in patients with CP infection.

Aged↗
PubMed2005

The eNOS gene polymorphism does not have a major impact on lipid parameters and premature coronary artery disease in Slovene men (Caucasians).

eNOS affects the NO level in the blood vessel wall, and therefore eNOS might be considered as a candidate gene for CAD. In this cross-sectional case-control association study we tested the hypothesis whether the eNOS 4alb gene polymorphism is a genetic marker for premature CAD in Slovene men. The eNOS 4a/b gene polymorphism was tested in 403 Slovene men: 215 cases with premature CAD and 188 subjects with no history of CAD. The frequency of 4a/b genotypes did not differ between patients and controls: in CAD patients the frequencies of the 4aa, 4ab, or 4bb genotype were 5.0%, 27.9%, or 67.1%, respectively, and in controls the genotype frequencies were 5.3%, 30.9%, or 63.8%, respectively. In this study the aa genotype of the eNOS 4a/b polymorphism was not associated with premature CAD (OR = 1, 95% CI 0.4-2.3, P = 0.9). Moreover, there were no differences in lipid parameters (total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides) between the subjects with the aa genotype and the subjects with the ab or bb genotype. In conclusion, we failed to demonstrate that the eNOS 4a/b gene polymorphism was a genetic marker for premature CAD in Slovene men.

Age of Onset↗
PubMed2003

Cytokine gene polymorphisms and the susceptibility to liver cirrhosis in patients with chronic hepatitis C.

BACKGROUND: The speed of fibrosis progression varies considerably between patients with chronic hepatitis C. This study analyzed whether cytokine gene polymorphisms are associated with a progressive course of the disease. METHODS: Leukocyte DNA from 101 patients with chronic hepatitis C, 52 patients with hepatitis C virus (HCV)-induced cirrhosis and 200 Caucasian blood donors was prepared. Using PCR, RFLP and PAGE, gene polymorphism analysis of the interleukin (IL)1alpha( - 889), IL1beta( - 511 and +3954), IL1 receptor agonist (RA)(intron2 VNTR), IL4(intron3 VNTR) and TNFalpha( - 308) loci was performed. RESULTS: Of the polymorphisms analyzed, IL1beta( - 511) and IL1RA(intron2 VNTR) were unevenly distributed between the study groups. The IL1 (- 511)*A2A2 genotype occurred significantly more often in chronic hepatitis C and HCV-induced liver cirrhosis than in the controls (P < 0.01, P < 0.05, respectively). Patients with HCV-induced cirrhosis displayed a significantly higher frequency of the IL1RA(intron2 VNTR)*A2 polymorphism than patients with chronic hepatitis C and controls (P < 0.05). CONCLUSIONS: Although the IL1beta( - 511)*A2A2 genotype may increase the susceptibility to acquire chronic hepatitis C and IL1RA(intron2 VNTR)*A2 polymorphism is associated with disease progression to cirrhosis, our results indicate that the analyzed cytokine gene polymorphisms have an overall low impact on the natural course of chronic hepatitis C infection.

Cytokines↗
PubMed1997

Renin-angiotensin system gene polymorphisms and left ventricular hypertrophy. The case against an association.

There is accumulating evidence for association between genetic polymorphisms of components of the renin angiotensin system (RAS), especially angiotensin-converting enzyme (ACE), and cardiovascular disease. However, there is lack of agreement that the ACE polymorphism is associated with left ventricular hypertrophy (LVH) in hypertension. A possible paradigm for the development of LVH involves the ACE gene polymorphism influencing cardiac mass by an action on plasma and/or tissue levels of angiotensin II. Such a model has experimental support and provides the basis for examining the lack of agreement between studies. The finding of lack of association between RAS gene polymorphism and LVH may be due to methodological problems, differences in genetic background between populations, interactions between genetic variants of RAS components or to the model being inappropriate. Low predictability of ACE genotype markers for LVH together with conflicting reports on the influence of RAS genetic variants on angiotensin II production suggests that the simple RAS paradigm may not apply for hypertension. Further information on the nature of the link between the ACE polymorphism and ACE regulation as well as the relation between the RAS and pathophysiology of LVH is needed. At present there is insufficient evidence to accept ACE gene polymorphism as a susceptibility marker for LVH.

Angiotensin II↗
PubMed2006

Impact of TGFbeta1 gene polymorphisms on acute and chronic rejection in pediatric heart transplant allografts.

BACKGROUND: The aim of this study was to assess the influence of IL-10 and TGFbeta1 gene polymorphisms on the development of acute rejection and coronary disease in pediatric heart transplant recipients. METHODS: Patients were classified as either Rejectors or Nonrejectors. Coronary artery disease (CAD) was diagnosed by angiography or on macroscopic examination. Genotyping PCR-SSP were performed for IL-10 and TGFbeta1 (codon 10 and 25) in 111 patients. Thirty-nine were Rejectors and 31 developed CAD. RESULTS: The proportion of IL-10 low-producers was higher in Rejectors than in Nonrejectors (respectively 46% versus 22%, P=0.009). IL-10 gene polymorphism was not associated with CAD. TGFbeta1-codon10-25 high-producers were 92.3% in Rejectors and 75% in Nonrejectors (P=0.026), 93.5% in patients with CAD and 76.2% in patients free from CAD (P=0.037). TGFbeta1-codon25 high-production separately analyzed correlated with CAD (31/31 high-producers in CAD=100% versus 69/80 in noCAD patients=86.2%, P=0.03). TGFbeta1-codon10 gene polymorphisms were not associated with CAD. CONCLUSION: IL-10 low-producers have an increased risk of acute rejection. High-expressors of TGFbeta1-codon10-25 have an increased risk of acute rejection and CAD, while TGFbeta1-codon25 high-production is associated with coronary disease. Genetic polymorphism may reveal patients at high-risk in whom therapies and monitoring should be adjusted.

Adolescent↗
PubMed2003

Cytokine gene polymorphisms moderate responses to respiratory syncytial virus in adults.

Immune responses and illness severity during viral upper respiratory infections may be influenced by the local elaboration of cytokines. Cytokine gene polymorphisms moderate immune responses and severity of illness in various inflammatory and infectious diseases. We performed cytokine genotyping on 29 adults experimentally inoculated with respiratory syncytial virus (RSV) to determine whether specific cytokine gene polymorphisms are associated with immune responses or illness severity. DNA was extracted from leukocytes and assayed for TNF-alpha, IFN-gamma, IL-6, IL-10 and TGF-beta1 genotypes using polymerase chain reaction-sequence-specific primer technology. Outcomes consisted of baseline and convalescent RSV-specific serum IgG and nasal IgA titers, nasal secretion weights, nasal, throat and general symptom scores, and nasal cytokine protein levels. IFN-gamma genotype was directly related with the frequency of subjects having at least a four-fold increase in RSV-specific serum IgG and TNF-alpha genotype was inversely associated with the frequency of subjects having at least a twofold increase in RSV-specific nasal IgA. Additionally, IL-6 genotype was predictive of certain measures of illness expression, while IFN-gamma genotype predicted IL-1 protein levels, and TNF-alpha genotype predicted IL-6 and IL-8 protein levels in nasal lavage fluids. There were no associations between IL-10 or TGF-beta1 and any of the outcome parameters. These results suggest that certain cytokine gene polymorphisms moderate immune responses and illness severity in adults experimentally exposed to RSV.

Adult↗
PubMed2006

Coagulase gene polymorphism of Staphylococcus aureus isolated from goat mastitis in Brazilian dairy herds.

AIMS: To investigate the coagulase gene polymorphism of Staphylococcus aureus isolated from mastitic goat's milk. METHODS AND RESULTS: A typing procedure based on coagulase gene polymorphism was used to discriminate S. aureus isolated from goat mastitis. Thirty-six strains collected from goats belonging to herds from northern Ceara State and Serrana region of Rio de Janeiro State were analysed. Based on restriction fragment length polymorphism of 3' end coagulase gene, the goat strains were grouped into 11 types. In northern Ceara herds, the predominant type was found in 60% of the strains, while in the Serrana region herds the two most common accounting for 62.5% of the strains. CONCLUSIONS: The analysis of the coa gene proved to be useful for typing S. aureus from goat mastitis. Although the results showed that goats from the studied regions were infected by S. aureus strains harbouring more than one coagulase genotype, only one or two types predominated. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of the prevalent strains within a herd or region is a necessity. The important virulence factors could be identified in such strains and this information can then be used as a specific base to develop S. aureus mastitis control measures.

Animals↗
PubMed2003

Gene polymorphism and folate metabolism: a maternal risk factor for Down syndrome.

The high birth frequency of Down syndrome (DS), trisomy 21 (T21), has been a subject of interest to the clinicians and researchers due to its complexity in phenotypic expression. In addition to the maternal age, identification of the mechanistic basis for T21 requires an understanding of the cellular-molecular events and other biochemical pathways that could promote maternal meiotic nondisjunction. Recent studies have linked the increased frequency of polymorphism of methylenetetrahydrofolate reductase (MTHFR, C677T) and methionine synthase gene (MTRR, A66G) in mothers with DS child. Based on evidence that abnormal folate and methyl metabolism can lead to DNA hypomethylation and abnormal chromosomal segregation, researchers have observed that mothers with mutation in MTHFR (C677T) and MTRR (A66G) gene have elevated levels of plasma homocysteine. This was found to be associated with a 2.6 to 2.9 fold increased risk of having child with DS compared to mothers without the mutation. Subsequent studies evaluating Italian, Irish, French, and Indian-Gujarati women could not demonstrate an association of MTHFR gene polymorphism in mothers with DS child. However, the Irish study did find an increased risk of DS associated with the MTRR polymorphism and an interactive effect of MTRR and MTHFR polymorphisms with increased risk. Interestingly, an increase in plasma homocysteine was found to be a risk factor for DS in several of the studies. Despite the differences, the published studies suggest a common theme of abnormal folate metabolism associated with increased risk of having a child with DS. These observations suggest that there seems to be a geographic variation in gene polymorphism and it could not be attributable to meiotic nondysjunction in all mothers with DS child but increased homocysteine in all different study group does suggest that there may be a gene-nutritional or gene-gene or gene-nutritional-environmental factors involved in increased frequency of meiotic nondisjunction which needs transnational and multinational study design.

Down Syndrome↗
PubMed2005

Age-related increase of pulse pressure and plasminogen activator inhibitor-1 I/D gene polymorphism in essential hypertension.

BACKGROUND: Pulse pressure (PP), a marker of cyclic strain on the arterial wall, is a significant predictor of cardiovascular (CV) risk, particularly regarding the incidence of coronary arterial stenosis. Genes related to haemostatic and/or fibrinolytic factors are consistently influenced in vitro by mechanical strain. OBJECTIVE: The goal of the present study was to determine, in the three genotypes of the plasminogen activator inhibitor (PAI)-1 gene polymorphism, the gender-adjusted difference in the relationships between age and PP in subjects with never treated essential hypertension. RESULTS: In the studied population, the genotype deletion (D)/D at position -675 of the PAI-1 insertion (I)/D gene polymorphism was associated with a significant increase in the adjusted slope of the curve relating age to PP by comparison with the two other genotypes. No comparable difference in age-related changes in systolic, diastolic or mean blood pressure was found. CONCLUSION: In subjects with essential hypertension, the PAI-1 I/D gene polymorphism modulates the age-mediated increase of PP, suggesting new insights on the complex interactions between genes, mechanical factors and CV risk.

Adult↗
PubMed2002

Interleukin-10, interleukin-6 and interferon-gamma gene polymorphisms in melanoma patients.

The immune response against melanoma can be influenced by cytokines with potentially opposite effects on tumour cell growth, such as interleukin-10 (IL10), interleukin-6 (IL6) and interferon-gamma (IFNgamma). Our objective in this study was to investigate whether polymorphisms in the regulatory regions of IL10, IL6 and IFNgamma genes are associated with the development of primary cutaneous melanoma and/or the prognosis of this tumour. We studied genotypic variations at positions -1082, -819 and -592 in the IL10 promoter, -174 in the IL6 promoter and +874 in the IFNgamma intron 1 in 42 melanoma patients and 48 healthy controls. These two populations showed very similar genotypic frequencies for IL10, IL6 and IFNgamma gene polymorphisms. There was a significant increase in the prevalence of IL10 low expression genotypes, specially the ACC/ATA genotype, among patients with a poorer prognosis. In contrast, IL6 promoter and IFNgamma intron 1 gene polymorphisms did not correlate with melanoma prognosis. These data indicate that investigation of polymorphisms in the regulatory regions of IL10, IL6 and INFgamma genes does not seem to be useful for predicting the risk of development of primary cutaneous melanoma. However, IL10 low expression genotypes may be associated with a poorer outcome in melanoma patients.

Adult↗
PubMed2004

Association of bone mineral density with vitamin D and estrogen receptor gene polymorphisms during GnRH agonist treatment.

AIMS: This study examined whether or not a decrease in bone mineral density (BMD) induced by the use of gonadotropin-releasing hormone agonist (GnRHa) during sexual maturation is affected by vitamin D receptor and/or estrogen receptor gene polymorphisms, like the phenomenon observed during the postmenopausal period. METHODS: In 43 patients who received GnRHa therapy for 6 months to treat uterine myoma or endometriosis at our department and who were confirmed to have pituitary down-regulation, we measured bone density before and after GnRHa treatment using DXA and analyzed the bone metabolism turnover using bone metabolic markers. Polymorphisms were analyzed by RFLP using FokI and TaqI for the vitamin D receptor gene and PvuII and XbaI for the estrogen receptor gene. The then determined gene polymorphism was analyzed in relation to the percentage decreases in BMD following GnRHa treatment. RESULTS: The patients were divided by f, t into two groups: (f, t) < 2 (Group V-I) and (f, t) > or = 2 (Group V-II). They were also divided by P, x into two groups (P, x) < 3 (Group E-I) and (P, x) > or = 3 (Group E-II). The BMD change was significantly higher in Group V-II than in Group V-I. Group E-II tended to have a higher BMD change than Group E-I, although this difference was not statistically significant. CONCLUSION: Patients who often have f and t polymorphism are more likely to show BMD reduction following GnRHa therapy, like the phenomenon seen during the postmenopausal period, than patients with other gene polymorphisms. Measures to avoid BMD reduction are required when using GnRHa in such patients.

Adult↗
PubMed2006

The relationship between hypertensive retinopathy and Angiotensin converting enzyme gene polymorphism.

OBJECTIVE: Hypertensive retinopathy is an important complication and a major site of target organ damage from hypertension. Angiotensin converting enzyme (ACE) has a main role in cardiovascular physiology. It was shown that ACE gene polymorphism is related to plasma concentrations of ACE. We aimed to investigate the relationship between ACE gene polymorphism and hypertensive retinopathy. METHODS: One-hundred and eight patients (62 female, mean age; 52.8 +/- 7.0 years) with essential hypertension and 30 healthy volunteers were enrolled in this study. Hypertensive retinopathy was diagnosed in a dark room with direct ophthalmoscopy by a single ophthalmologist who was blinded to clinical data. Polymerase chain reaction analysis was used to detect the insertion/deletion (l/D) polymorphism of the ACE gene. Patients were assigned to Group DD, Group ID and Group II. Three genotypic subgroups were compared for hypertensive retinopathy. RESULTS: There were 42 patients (27 female, mean age: 52.4 +/- 7.8) in DD group; 51 patients (28 female, mean age: 53.6 +/- 6.9) in ID group and 15 patients (7 female, mean age: 51.2 +/- 5.6) in II group. Basal characteristics of the patients were similar in the three groups. The genotypic distributions of patients and healthy controls were comparable. Hypertensive retinopathy was determined in 15 (35.7%) patients in DD group, 8 (15.6%) patients in ID group and 2 (13.3%) patients in II group (p<0.05). CONCLUSION: We found a significant relationship between ACE gene I/D polymorphism and hypertensive retinopathy. Identification of ACE genotype in hypertensive patients might be useful to discriminate the patients who are more susceptible to hypertensive retinopathy.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Association between xenobiotic gene polymorphisms and non-Hodgkin's lymphoma risk.

The last four decades have seen a significant increase in the incidence of non-Hodgkin's lymphoma (NHL) as a possible result of increasing environmental carcinogen exposure, particularly pesticides and solvents. Based on the increasing evidence for an association between carcinogen exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a case-control study of xenobiotic gene polymorphisms in individuals with a diagnosis of NHL. Polymorphisms of six xenobiotic genes (CYP1A1, GSTT1, GSTM1, PON1, NAT1, NAT2) were characterized in 169 individuals with NHL and 205 normal controls using polymerase chain reaction-based methods. Polymorphic frequencies were compared using Fisher's exact tests, and odds ratios for NHL risk were calculated. Among the NHL group, the incidence of GSTT1 null and PON1 BB genotypes were significantly increased compared with controls, 34% vs 14%, and 24% vs 11% respectively. Adjusted odds ratios calculated from multivariate analyses demonstrated that GSTT1 null conferred a fourfold increase in NHL risk (OR = 4.27; 95% CI, 2.40-7.61, P < 0.001) and PON1 BB a 2.9-fold increase (OR = 2.92; 95% CI, 1.49-5.72, P = 0.002). Furthermore, GSTT1 null combined with PON1 BB or GSTM1 null conferred an additional risk of NHL. This is the first time that a PON1 gene polymorphism has been shown to be associated with cancer risk. We conclude that the two polymorphisms, GSTT1 null and PON1 BB, are common genetic traits that pose low individual risk but may be important determinants of overall population NHL risk, particularly among groups exposed to NHL-related carcinogens.

Arylamine N-Acetyltransferase↗
PubMed2005

LMP7/TAP2 gene polymorphisms and HPV infection in esophageal carcinoma patients from a high incidence area in China.

Esophageal carcinoma is characterized by a widely ranged incidence variation among the different geographic regions. Anyang is a county in Henan Province of North China with the highest prevalence of esophageal carcinoma. Human papillomavirus (HPV) infection has been linked to the etiology of esophageal cancer in this area. In this study, we investigated correlations of the polymorphisms at low molecular weight polypeptide (LMP) and transporters with antigen processing (TAP) genes, with the risk of esophageal carcinoma. DNA extracted from either tumor specimens or esophageal epithelial cells was used to test HPV infection. Peripheral blood lymphocyte DNA was used for LMP/TAP genotyping. Polymerase chain reaction was performed to analyze HPV infection and LMP/TAP gene polymorphisms. The combined effect of LMP/TAP gene polymorphisms and HPV infection on esophageal carcinoma was analyzed by using unconditional logistic regression models. The TAP2 codons 379 isoleucine carriers and LMP7 codons 145 lysine carriers were found to be more susceptible to esophageal carcinoma (OR = 2.74, 95% CI = 1.15-6.49, P = 0.023 for TAP2; OR = 2.19, 95% CI = 1.09-4.37, P = 0.027 for LMP7). Patients carrying homozygous LMP7/TAP2 haplotype C, which contained the glutamine at LMP7 codons 145 and the isoleucine at TAP2 codons 379, were more prone to develop esophageal carcinoma (OR = 2.96, 95% CI = 1.13-7.81, P = 0.027). An additive effect on the risk of esophageal carcinoma development was found among individuals carrying LMP7/TAP2 haplotype C and infected by HPV (OR = 4.33, 95% CI = 2.53-7.42, P < 0.0001). LMP7/TAP2 haplotype C may act as the risk factor in esophageal carcinoma development and it may influence the tumorigenesis in HPV infected individuals.

Adult↗
PubMed2002

Lack of association of alpha-1 antichymotrypsin gene polymorphism with PR3-ANCA and MPO-ANCA associated vasculitis.

In patients with PR3-ANCA associated vasculitides the carrier frequency of alpha1-antitrypsin (AAT) deficiency allele PI*Z is increased and linkage disequilibrium between polymorphic markers within a cluster of serine protease inhibitor (serpin) genes, including AAT gene, at chromosome 14q32.1 has been described. A1-antichymotrypsin (AACT), part of an extended serpin gene cluster, was discussed to contribute to PR3-ANCA associated vasculitis formation. To analyse, if an AACT gene polymorphism within the signal peptide sequence is associatedwith antineutrophil cytoplasm autoantibodies (ANCA) vasculitis allelic frequencies of AACT polymorphism were analysed in 128 control persons, 79 PR3-ANCA, and 30 MPO-ANCA patients. In MPO-ANCA patients also phenotyping of AAT was performed as well as frequency and linkage analysis of simple tandem repeat polymorphisms in the genes of cortisol-binding globulin, AAT, protein C inhibitor, and three extragenic markers (S48, S55, S51) of the gene cluster. Allelic frequencies of the AACT polymorphism did not differ between controls and vasculitis patients. In the MPO-ANCA group no patient expressed the Pi*Z defective allele of AAT and the allelic frequencies of polymorphic markers within the serpin gene cluster did not differ from those of the controls. Strong linkage disequilibrium was detected in MPO-ANCA patients neither. Therefore, we can not support the hypothesis that AACT polymorphism contributes to the pathogenesis of PR3-ANCA vasculitis. Nor is it probable that any factor, coded by the serpin gene cluster, contributes to MPO-ANCA vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2005

Association of functional gene polymorphisms of matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9 with the progression of chronic liver disease.

BACKGROUND AND AIMS: Matrix metalloproteinases (MMP) play an important role in the progression of liver fibrosis in addition to fibrogenesis. MMP-1, MMP-3, and MMP-9 gene polymorphisms have been shown to influence the transcriptional activity of their respective gene promoter in an allele-specific manner. The aim of this study was to examine the possible association of MMP-1, MMP-3, and MMP-9 gene polymorphisms with the progression of chronic liver disease in the Japanese population. METHODS: We examined 91 patients with HCV-related chronic hepatitis and 89 patients with HCV-related liver cirrhosis. We determined MMP-1 1G/2G, MMP-3 5A/6A, and MMP-9 C/T polymorphisms using polymerase-chain reaction based assays. RESULTS: In MMP-1 genotypes, the 2G homozygotes were significantly more in cirrhotic group than in chronic hepatitis group. In MMP-3 genotypes, there were no significant differences in genotype distributions and allele frequencies between chronic hepatitis and liver cirrhosis groups. However, 5A carriers had a significantly lower age at liver cirrhosis diagnosis and a higher Child-Pugh score compared with the 6A homozygotes. In MMP-9 genotypes, the C homozygotes and C allele frequencies were significantly more in liver cirrhosis group than in chronic hepatitis group. CONCLUSION: These findings suggest that MMP-1, MMP-3, and MMP-9 gene polymorphisms account for some of the variability in the progression of HCV-related chronic liver diseases.

Aged↗