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PubMed2002

Variation in the lipoprotein receptor-related protein, alpha2-macroglobulin and lipoprotein receptor-associated protein genes in relation to plasma lipid levels and risk of early myocardial infarction.

BACKGROUND: The lipoprotein receptor-related protein (LRP) is an endocytic receptor for several ligands, such as alpha2-macroglobulin (alpha2 M) and apolipoprotein E. LRP is involved in the clearance of lipids from the bloodstream and is expressed in the atherosclerotic plaque. The LRP-associated protein (LRPAP in humans, RAP in mice) acts as a chaperone protein, stabilizing the nascent LRP peptide in the endoplasmic reticulum and Golgi complex. In mice, the amount of LRP activity was modulated by RAP, and RAP-null mice showed higher levels of total cholesterol. OBJECTIVE: To evaluate the association between DNA polymorphisms at the LRP, LRPAP and alpha2 M genes and early myocardial infarction (MI). METHODS: We genotyped 210 patients with early MI (<55 years) and 200 healthy control participants for three polymorphisms in the LRP, LRPAP and alpha2 M genes. RESULTS: No association was found between these polymorphisms and plasma lipid levels in patients and control participants. Only the LRPAP-intron 1 polymorphism (a 21 bp insertion/deletion) was associated with MI (P = 0.0065; odds ratio = 2.18, 95% confidence intervals = 1.22-3.90). CONCLUSIONS: According to our data, the variation at the LRPAP1 gene could contribute to the risk of developing an early episode of MI.

Adult↗
PubMed2005

Interleukin-1-beta gene, but not the interleukin-1 receptor antagonist gene, is associated with Graves' disease.

Interleukin-1 (IL-1) is considered to be involved in the pathogenesis of Graves' disease. The aim of this study was to test whether the IL-1-beta gene promoter region and exon 5 and IL-1 receptor antagonist (IL-1Ra) gene intron 2 polymorphisms could be useful genetic markers for susceptibility to Graves' disease. A normal control group of 163 healthy people and another group of 95 patients with Graves' disease were examined. Polymerase chain reaction (PCR) was used to analyze the variable number of tandem repeats (VNTRs) at intron 2 of the IL-1Ra gene for the polymorphism. PCR-based restriction analysis was done for the IL-1-beta gene polymorphisms of the promoter region and exon 5 using endonucleases AvaI and TaqI, respectively. We found significantly increased frequencies of the C/C homozygous genotype (chi(2) test, P=0.038; odds ratio (OR)=2.558, 95% confidence interval (CI)=1.205-5.430) and the C allele (chi(2) test, P=0.011; OR=1.589, 95% CI=1.094-2.309) in the IL-1-beta gene promoter (-511 C/T polymorphism) in Graves' disease patients compared to normal controls. There were no significant differences in polymorphisms of IL-1-beta gene exon 5 and IL-1Ra gene intron 2 between the patient and normal control groups. A subgroup analysis also demonstrated no association between the severity of the disease and any polymorphism of IL-1-related genes. We suggest that the IL-1-beta gene promoter polymorphism can be used as a genetic marker for susceptibility to Graves' disease. It is worthwhile to study the cytokine genes further because of the association between cytokines and Graves' disease.

Adolescent↗
PubMed2000

Vitamin D receptor polymorphisms are associated with altered prognosis in patients with malignant melanoma.

Calcitriol [1,25(OH)2D3], the hormonal derivative of vitamin D3, is an antiproliferative and prodifferentiation factor for several cell types, including cultured melanocytes and malignant melanoma (MM) cells. Several polymorphisms of the vitamin D receptor (VDR) gene have been described including a FokI RFLP in exon 2, BsmI, and ApaI polymorphisms in intron 8 and an adjacent TaqI RFLP in exon 9. Alterations in vitamin D/1,25(OH)2D3 levels and polymorphisms of the VDR have been shown to be associated with several systemic malignancies. We hypothesize that polymorphism in this gene may be associated with altered susceptibility and outcome in patients with MM. A hospital-based case-control study, using 316 MM cases and 108 controls, was used to assess associations with MM susceptibility. Breslow thickness, the most important single prognostic factor in MM, was used as the outcome measure. Polymorphisms at the FokI and TaqI restriction sites were determined using PCR-based methods. Polymorphism at the FokI, but not TaqI, RFLP was associated with an altered risk of MM (P = 0.014). More importantly, variant alleles were associated with increased Breslow thickness. Thus, homozygosity for variant alleles at both RFLP (ttff genotype combination) was significantly associated with thicker tumors. (> or = 3.5 mm; P = 0.001; odds ratio = 31.5). Thus, polymorphisms of the VDR gene, which would be expected to result in impaired function, are associated with susceptibility and prognosis in MM. These data suggest that 1,25(OH)2D3, the ligand of the VDR, may have a protective influence in MM, as has been proposed for other malignancies.

Case-Control Studies↗
PubMed2003

Genetic polymorphisms of serotonin and dopamine transporters in mental disorders.

Transporter-assisted uptake of serotonin (5-HT) and dopamine (DA) has been accounted for activities in human behavior or mental status, because they are the sites of action of widely used antidepressant and psychoactive drugs. Both the human serotonin transporter (5-HTT) and human dopamine transporter (DAT1) genes are good candidates for etiological involvement in various psychiatric conditions. The serotonin transporter gene has two types of functional polymorphisms. One is serotonin transporter linked polymorphic region (5-HTTLPR) consisting of length variation of the repetitive sequence containing 20-23-bp-long repeat elements in the 5'-upstream region of the gene. Another polymorphism is that serotonin transporter variable number of tandem repeats (5-HTTVNTR) in its second intron. Both polymorphisms affect the transcription ratio of 5-HTT gene and may modify neuronal transmission by changing its protein expression. On the other hand, DAT1 gene has a variable number of tandem repeats type polymorphism (DAT1VNTR) in the 3'-untranslated region of the mRNA, which was also reported to change its gene expression. So polymorphic variations of transporters would change the behavioral and neuropathological tendency. Here, the feature of those two transporters and their relations to psychiatric disorders are described.

3' Untranslated Regions↗
PubMed1993

A database of polymorphisms in the von Willebrand factor gene and pseudogene. For the Consortium on von Willebrand Factor Mutations and Polymorphisms and the Subcommittee on von Willebrand Factor of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis.

Nucleotide sequence polymorphisms in the von Willebrand factor (vWF) gene are useful for genetic studies in von Willebrand disease (vWD). This database describes 33 known vWF polymorphisms distributed throughout the vWF gene. DNA sequence information is available for 21 of these sites. The most informative system is a tetranucleotide repeat polymorphism in vWF intron 40. Sixteen of these polymorphisms are within vWF exons, and approximately half of them also alter the encoded amino acid sequence. Many occur close to mutations that cause vWD. The high prevalence of vWF polymorphisms must be considered in the analysis of candidate vWD mutations. In addition to the vWF gene on chromosome 12, there is a partial unprocessed vWF pseudogene on chromosome 22 that corresponds to vWF exons 23 to 34. Three polymorphisms have been assigned to the vWF pseudogene. Because the vWF gene and pseudogene have diverged only approximately 3.1% in DNA sequence, correct assignment of polymorphisms to either locus can be difficult in the region of homology. This problem has been solved in some cases by comparison of the published sequences and predicted restriction maps for the gene and pseudogene.

DNA Mutational Analysis↗
PubMed2002

The LDL receptor-related protein (LRP1/A2MR) and coronary atherosclerosis--novel genomic variants and functional consequences.

The LDL receptor-related protein/alpha 2-macroglobulin receptor (LRP1/A2MR) is a multifunctional cell-surface glycoprotein that endocytoses several structurally and functionally distinct ligands. In clinical studies different genomic variants of the LRP1/A2MR and its role in the development of degenerative diseases like atherosclerosis or Alzheimer's disease were studied. We screened for novel genomic variants of LRP1/A2MR and investigated the importance of these variants in 214 coronary patients suffering from myocardial infarction as well as in 224 healthy controls. We detected a novel C>G polymorphism at position -25 in the functionally important promoter region of LRP1/A2MR. This polymorphism (c.1-25C>G) leads to the creation of a new GC-box, recognized by the constitutively expressed SP 1 transcription factor. Investigating the LRP1/A2MR gene expression with respect to this polymorphism, carriers of the mutant G-allele were found to have a higher mRNA expression level. A novel polymorphism in exon 22 (c.4012C>T), and two novel polymorphisms in intron 24 (IVS24+123C>A and IVS24+690G>A) associated with a previously described polymorphism in exon 61 (c.10249G>A), were related to the development of myocardial infarction. Two novel rare genetic variants of exon 88 (c.13933C>T) and intron 88 (IVS88+15G>A) were identified in four patients with severe coronary symptoms. However, the LRP1/A2MR gene expression was found to be independent of all identified novel genomic variants as well as other previously described changes (A217V, A775P, D2080N, D2632E, G4379S) except the promoter polymorphism.

Adult↗
PubMedDate not supplied

[Pulmonary carcinogenesis susceptibility-associated single-nucleotide polymorphisms in K-ras intron 2 affect the binding of factor Gata-6 but not gene expression].

The sequence of K-ras intron 2, which has been associated with lung tumor susceptibility in inbred mouse strains, was analyzed in susceptible strain GR and in resistant strains PT and UT. In the latter case, the intron had a tandem repeat of a 37-bp sequence with variant GC of its two single-nucleotide polymorphisms (SNPs), as earlier reported for resistant strains AKR, C57BL/c, and C3H/A. Strain GR did not differ in intron structure from susceptible strains A/He and ICR, having one copy of the 37-bp sequence with SNP variant CA. By gel retardation assay, a DNA probe corresponding to "susceptible" allele CA of K-ras region 278-307 formed an additional complex with nuclear proteins extracted from the lungs, as compared with probes corresponding to the "resistant" GC and "intermediate" CC alleles. With specific antibodies, the protein binding to the susceptible allele was identified as transcription factor GATA-6. Reverse transcription with subsequent multiplex PCR did not reveal a significant difference in K-ras expression for susceptible and resistant strains. The results suggest that SNPs of K-ras intron 2 do not affect the level of K-ras expression but do control the binding of GATA-6, which plays an important role in lung differentiation.

Animals↗
PubMed2006

Association of the human urate transporter 1 with reduced renal uric acid excretion and hyperuricemia in a German Caucasian population.

OBJECTIVE: Human urate transporter 1 (hURAT1) is a member of the organic anion transporter family (SLC22A12) that mainly regulates tubular urate reabsorption. Loss-of-function mutations result in idiopathic hypouricemia. The present case-control study was designed to analyze whether hURAT1 might also be a candidate gene for hyperuricemia with primary reduced renal urate excretion. METHODS: DNA samples from 389 individuals with reduced fractional excretion of uric acid (FEUA) (< or =6.5%) and from 263 controls (FEUA >6.5%) were sequenced. Genotype frequencies between groups were compared by Cochran-Armitage trend test. RESULTS: Significantly different genotype distributions could be demonstrated for the -788 T >A (promoter; P = 0.014), the C258T (exon 1; P = 0.006), and the C426T (exon 2; P = 0.0002) polymorphisms, but not for the T1309C (exon 8) and the +18 C >T (intron 9) polymorphisms. The strongest association with reduced FEUA was observed for the C426T polymorphism, with odds ratios (ORs) of 1.59 and 2.54 (P = 0.0002) for the CT and TT genotypes, respectively. Adjusted values for FEUA in the C426T genotype, were significantly reduced decreasing to 7.3%, 6.7%, and 6.3% in individuals with the CC, CT, and TT genotypes, respectively (P = 0.004). Haplotypes were constructed from the -788 T >A, C258T, and C426T polymorphisms. Individuals carrying at least 1 ACT haplotype (n = 349) had a significantly higher risk for reduced FEUA than individuals without any ACT haplotype (n = 303) (OR 1.39, P = 0.041). CONCLUSION: These results indicate that polymorphisms in the N-terminus of the hURAT1 gene were significantly associated with reduced renal uric acid excretion. The main regulating factor seems to be located close to the C426T polymorphism or is in strong linkage disequilibrium.

Adult↗
PubMed2005

Microsatellite polymorphisms in the epidermal growth factor receptor (EGFR) gene and the transforming growth factor-alpha (TGFA) gene and risk of oral cancer in Puerto Rico.

OBJECTIVES AND METHODS: Risks of oral cancer related to a CA microsatellite repeat polymorphism in intron 1 of the epidermal growth factor receptor (EGFR) gene and a TaqI polymorphism in the transforming growth factor-alpha (TGFA) gene were evaluated in a population-based case-control study consisting of 157 cases and 149 controls recruited in Puerto Rico. RESULTS: Carriers of > or = 16 CA repeats in EGFR showed a 1.9-fold increased risk for oral cancer (OR=1.9, 95% CI=1.0-3.5). Risks also tended to increase with decreasing number of alleles with > or = 16 CA repeats (P for trend=0.06). Our data suggested a non-significant reduction in risk for subjects heterozygous for the TGFA polymorphism (OR=0.6, 95% CI=0.2-1.3). CONCLUSIONS: The EGFR-associated risk appeared to be independent of tobacco and alcohol use and may be restricted primarily to subjects who consumed low amounts of fresh fruits and vegetables (OR=5.9, 95%CI: 2.3-15.2). These data implicate dietary and molecular targets for oral cancer prevention.

Adult↗
PubMed2005

A new case of congenital goiter with hypothyroidism caused by a homozygous p.R277X mutation in the exon 7 of the thyroglobulin gene: a mutational hot spot could explain the recurrence of this mutation.

Identification of thyroglobulin (TG) gene mutations may provide insight into the structure-function relationship. In this study, we have performed molecular studies in a patient with congenital goiter, hypothyroidism, and impairment of TG synthesis. Genomic DNA sequencing revealed a homozygous c.886C-->T mutation in exon 7, resulting in a premature stop codon at amino acid 277 (p.R277X). The same nonsense mutation had been reported previously in two Brazilian families with multiple occurrence of congenital hypothyroidism with goiter. We compared the insertion/deletion polymorphism in intron 18, microsatellites (Tgm1, Tgm2, TGrI29, and TGrI30), and exonic single-nucleotide polymorphism haplotypes identified in the patient with a member of the previously reported family, who also carry the mutation as a compound heterozygous mutation. The single-nucleotide polymorphism and microsatellite analysis revealed that the two affected individuals do not share a common TG allele. This suggests that the p.R277X mutation is a mutational hot spot. No difference in either splicing or abundance of the amplified product was detected by RT-PCR, excluding that an alternative splicing mechanism, by skipping of exon 7, would restore the normal reading frame. In conclusion, we report a new case of congenital goiter and hypothyroidism caused by a p.R277X mutation in the TG gene. Moreover, we show that nucleotide 886 is a mutational hot spot that explains the recurrence of this mutation.

Amino Acid Sequence↗
PubMed1999

Little evidence of HLA-G mRNA polymorphism in Caucasian or Afro-Caribbean populations.

HLA-G is a nonclassical class I MHC molecule of unknown function expressed on human trophoblast. The level of polymorphism at the HLA-G locus is of considerable importance, since the paternally inherited gene product is exposed to the maternal immune system during pregnancy. However, previous studies of HLA-G polymorphism using genomic DNA samples have produced conflicting results. Our aim was to investigate polymorphism in trophoblast HLA-G mRNA from pregnancies in ten Caucasian and twelve Afro-Caribbean women by RT-PCR. A similar PCR protocol was also applied to umbilical cord blood genomic DNA from two Caucasian and two Afro-Caribbean neonates. Caucasian cDNA yielded only two different sequences: G*01011, and one containing a previously reported synonymous substitution. Afro-Caribbean samples yielded these sequences as well as one previously reported conservative (leucine-to-isoleucine) substitution. PCR amplification from genomic DNA samples from both populations using previously published primer pairs generated sequences containing multiple substitutions, many of which were nonsynonymous. More than two sequences were produced from genomic DNA from each individual. In contrast, amplification from the same genomic DNA using new primers complementary to exons of the HLA-G gene yielded the same few sequences generated from cDNA. These results suggest that polymorphism at the HLA-G locus is extremely limited in Caucasian and Afro-Caribbean populations. This suggests that spurious polymorphism has been reported in African Americans due to the use of intron-complementary PCR primers on genomic DNA samples. The monomorphic nature of HLA-G may allow trophoblast to carry out the immunological functions of class I-bearing tissues without compromising successful pregnancy.

Africa↗
PubMed2004

Taq1B polymorphism of CETP gene on lipid abnormalities in patients with type II diabetes mellitus.

The most common alterations in lipid and lipoprotein metabolism in type 2 diabetes involve an elevation in both plasma triglyceride and VLDL concentrations, a dense LDL phenotype and low levels of HDL cholesterol. The inverse relationship between the level of HDL cholesterol and the risk of cardiovascular disease is commonly explained by the crucial role of HDL in reverse cholesterol transport. Cholesterol ester transfer protein (CETP) has a central role in the metabolism of HDL and may therefore alter the susceptibility to atherosclerotic vascular disease. To evaluate the effect of Taq1B polymorphism of intron 1 of CETP gene on serum lipid concentrations in Turkish type 2 diabetic patients, we investigated Taq1B polymorphism and serum lipid levels in 116 controls and in 164 diabetic patients. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the CETP Taq1B polymorphism. Serum lipid levels were measured enzymatically. Statistical analyses was performed by SPSS. In control group: subjects with B2B2 genotype have high HDL-cholesterol levels (p=0.029) and B1B1 genotypes have high triglyceride levels (p=0.07). Diabetic patients with and without MI with B2B2 genotype have high HDL-cholesterol levels. Taq B1B1 genotype has higher in diabetic patients with myocardial infarction (MI) than diabetic patients without myocardial infarction (42.1% and 32.7%; chi2=1.42, p=0.23). The present study demonstrates that the CETP Taq1B gene polymorphism is an association with low HDL cholesterol levels in patients with type II diabetes mellitus and healthy controls in Turkey. We also showed that CATE Taq1B gene polymorphism may be related to myocardial infarction in type II diabetic patients.

Aged↗
PubMed1989

DNA rearrangement and restriction fragment length polymorphism within the first BCR intron in Philadelphia-positive acute leukemia.

In some patients with Philadelphia (Ph)-chromosome positive acute lymphoblastic leukemias, breakpoints on chromosome 22 are reported to occur within the first BCR intron. To analyze the breakpoints in chromosome 22 of Ph-positive acute leukemia patients without rearrangement of the 5.8 kb bcr, we cloned the 3' part of the first BCR intron using a synthetic DNA probe. During the course of study, we mapped the region of the deletion/insertion of 1 kb that causes a restriction fragment length polymorphism (RFLP) and found a racial difference in the frequencies of the alleles giving rise to this RFLP. Analyses of the patients' samples indicated that breakpoints were located within the 8.5 kb EcoRl fragment of the first BCR intron in two of five Ph-positive acute leukemia patients. The data, together with the previous reports, indicate that breakpoints within this approximately 50 kb intron are widely scattered, in contrast to those confined within the 5.8 kb bcr in chronic myelogenous leukemias.

Acute Disease↗
PubMed2000

Genetic risk factors for coronary artery spasm: significance of endothelial nitric oxide synthase gene T-786-->C and missense Glu298Asp variants.

BACKGROUND: We recently identified two endothelial nitric oxide synthase (eNOS) gene polymorphisms, Glu298Asp and T-786-->C, which are independently associated with coronary spasm. eNOS gene intron 4b/a polymorphism is also reported to be involved in smoking-dependent coronary artery disease. The genetic linkage among these polymorphisms remains unknown. Also, it is unclear which variant is most responsible for coronary spasm. In the present study, we first examined the genetic linkage among these three variants. Next, we studied the risk factors of coronary spasm by using all significant genetic and conventional risk factors in a large-scale study. METHODS: The genotype and allele frequencies for the T-786-->C, intron 4b/a, and Glu298Asp variants were assessed in 423 randomly selected DNA samples to examine their genetic linkages. The relative capacities of all risk factors to predict coronary spasm were then analyzed using multiple logistic regression in 201 patients with coronary spasm and 345 volunteers. RESULTS: Comparison of allele frequencies revealed that the eNOS intron 4a allele was significantly linked to the T-786-->C mutation (P < 0.00001), whereas there was not a linkage between the intron 4a allele and the Glu298Asp variant (P = 0.1437) or between the Glu298Asp variant and the T-786-->C mutation (P = 0.1996). Multiple logistic regression revealed that the most predictive independent risk factor for coronary spasm was the T-786-->C mutation (P < 0.001), followed by cigarette smoking (P < 0.001), hypertension (P = 0.004), and the Glu298Asp variant (P = 0.028). CONCLUSIONS: We found that the T-786-->C mutation and the intron 4a allele are in linkage disequilibrium. We previously showed that the T-786-->C mutation reduced eNOS gene promoter activity. In that context, our results strongly suggest that the T-786-->C mutation underlies the functional characteristics of the intron 4a allele. Further, multiple logistic regression analysis revealed that the T-786-->C mutation is the most predictive risk factor for coronary spasm, followed by cigarette smoking. Given that those effects are potentially additive, patients carrying the eNOS gene variants should be strongly cautioned against smoking.

Adult↗
PubMed1993

Alterations of the Rb gene and its association with Ki-ras activation and p53 inactivation in endometrial adenocarcinoma.

Alterations of the retinoblastoma (Rb) gene were evaluated in nine primary endometrial adenocarcinomas that we had previously analyzed for the presence of Ki-ras activations and p53 alterations and in three endometrial carcinoma cell lines. Loss of mRNA expression in the Rb gene was detected in two of the 12 tumors. Internal deletions of Rb cDNA were observed in two tumors; one was a deletion of exon 21 in a primary carcinoma, and the other was a deletion of exon 8 in one allele in one cell line. Loss of heterozygosity of the Rb gene, which was detectable by polymorphisms in introns 1 and 17, was analyzed using polymerase chain reaction-restriction fragment length polymorphism analysis in 29 endometrial carcinomas. Of 13 heterozygous cases, two cases (15%) showed loss of heterozygosity. We therefore suggest that alteration of the Rb gene, as well as activation of the Ki-ras gene and alterations of the p53 gene, plays a significant role in the etiology of endometrial adenocarcinoma.

Adenocarcinoma↗
PubMed2000

Determination of the DNA sequences of acetylcholinesterase and butyrylcholinesterase from cat and demonstration of the existence of both in cat plasma.

Cat serum contains 0.5 mg/L of butyrylcholinesterase (BChE, EC 3.1.1. 8) and 0.3 mg/L of acetylcholinesterase (AChE, EC 3.1.1.7); this can be compared with 5 mg/mL and < 0.01 mg/L, respectively, in human serum. Cat BChE differed from human BChE in the steady-state turnover of butyrylthiocholine, having a 3-fold higher k(cat) and 2-fold higher K(m) and K(ss) values. Sequencing of the cat BCHE cDNA revealed 70 amino acid differences between cat and human BChE, three of which could account for these kinetic differences. These amino acids, which were located in the region of the active site, were Phe398Ile, Pro285Leu, and Ala277Leu (where the first amino acid was found in human and the second in cat). Sequencing genomic DNA for cat and human ACHE demonstrated that there were 33 amino acid differences between the cat and human AChE enzymes, but that there were no differences in the active site region. In addition, a polymorphism in intron 3 of the human ACHE gene was detected, as well as a silent polymorphism at Y116 of the cat ACHE gene.

Acetylcholinesterase↗
PubMed2001

Interleukin-10 and tumor necrosis factor gene polymorphisms and risk of coronary artery disease and myocardial infarction.

Inflammation plays an important role in the pathogenesis of atherosclerosis and acute coronary syndromes. Cytokines IL-10 and TNF-alpha exert opposite functions in inflammatory reactions, IL-10 acting predominantly as an antiinflammatory and TNF-alpha as a proinflammatory factor. Functional single nucleotide polymorphisms in the genes of IL-10, TNF-alpha, and TNF-beta are associated with gene expression and plasma levels of IL-10 and TNF-alpha. The aim of the study was to assess whether these IL-10 and TNF gene polymorphisms are related to the risk of coronary artery disease (CAD) and myocardial infarction (MI). Consecutive, angiographically examined patients with significant coronary stenoses but without symptoms or signs of old or acute MI constituted the group with CAD (n=998) and patients with old or acute MI constituted the group with MI (n=793). Subjects with neither angiographic CAD nor symptoms or signs of MI (n=340) served as controls. They were matched with the patients for age and sex. Genotyping was performed with techniques based on the polymerase chain reaction. Allele frequencies, genotype distributions, and frequencies of allele combinations for three IL-10 promoter polymorphisms, -1082G/A, -819C/T and -592C/A, were similar between CAD patients, MI patients, and matched controls. Similarly, genetic analysis did not reveal group-specific differences for the TNF-alpha promoter polymorphisms -863C/A and -308G/A, as well as for the TNF-beta intron 1 polymorphism 252G/A. In addition, no relationship was found between specific combinations of IL-10 and TNF alleles, indicative of low IL-10 and high TNF-alpha production, respectively, and CAD or MI. The lack of association persisted also after adjusting for other cardiovascular risk factors. Our findings suggest that six different and functionally relevant polymorphisms of the genes coding for IL-10, TNF-alpha, and TNF-beta are neither separately nor in cooperation associated with the risk of CAD or MI in angiographically examined patients.

Coronary Disease↗