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PubMed2002

[The relationship of beta-fibrinogen gene polymorphisms and ischaemic cardiocerebral vascular disease].

OBJECTIVE: To analyze the frequency of beta-fibrinogen (beta-Fg) gene -455G/A, -148C/T and 448G/A polymorphism, fibrinogen molecular reactivity and their association with plasma fibrinogen levels in health adults, myocardial infarction and cerebral infarction disease. METHODS: The beta-Fg gene -455G/A, -148C/T and 448G/A polymorphisms were analyzed by restriction fragment length polymorphism (RFLP). Fibrinogen molecular reactivity was analyzed for the conversion kinetics of fibrinogen into fibrin by a computer assistant procedure. Plasma fibrinogen levels were determined by Clauss method. RESULTS: The frequencies of -455A, -148T, 448A allele in health adults were 0.185, 0.194 and 0.192, in myocardial infarction disease 0.295, 0.318 and 0.307, in cerebral infarction disease 0.177, 0.193 and 0.182, respectively. The frequencies of -455A, -148T, 448A alleles in myocardial infarction disease were apparently higher than that of health adults. There were close linkage between -455G, -148C and 448G or -455A, -148T and 448A, the correspondence was over 98%. There are no differences in the plasma fibrinogen levels of the three polymorphisms in two genotype groups. The fibrinogen molecular reactivity was significantly increased in cardiocerebral vascular disease and related with plasma fibrinogen level. CONCLUSION: The three polymorphisms loci are strong linkage disequilibrium. There are no significant differences in the plasma fibrinogen levels of the three polymorphisms in two genotype groups. The frequencies of -455A, -148T, 448A alleles in myocardial infarction disease were apparently higher than that of health adults. It suggest that there was no association between beta-Fg gene -455G/A, -148C/T and 448G/A polymorphisms and plasma fibrinogen levels, but did in myocardial infarction disease. The fibrinogen molecular reactivity was significantly increased in cardiocerebral vascular disease and related with plasma fibrinogen level.

Adult↗

PubMed2002

[Study on the Relationship between susceptibility of stomach neoplasm cancer and polymorphism of inducible nitric oxide synthase gene].

OBJECTIVE: To study the relationship between polymorphism of inducible Nitric Oxide Synthase (iNOS) gene and the susceptibility of intestinal type stomach cancer and stomach cardia cancer in Chinese people. METHODS: A community-based case-control study was designed. Ninety-three intestinal type of stomach cancer and 50 stomach cardia cancer patients with endoscopy and pathology diagnosis were identified as cases. Two hundred and forty-six controls served as controls. RESULTS: C-->T polymorphism was found in exon 16 of iNOS gene, which changed the coding amino acid from serine to leucine, and formed a recognition site identified by Tsp 509 I restriction enzyme (we called it C-->T polymorphism). The T allele gene frequency in the control group was 13.21%. No statistically significant difference was found between C-->T polymorphism alone and the increased susceptibility to intestinal stomach cancer or stomach cardia cancer. A significant type 2 multiplicative interaction was found in increasing both the risk of intestinal stomach cancer and stomach cardia cancer when both C-->T polymorphism and tobacco smoking exposure existed. An additive interaction model, which showed statistically significant difference, was found to increase only the risk of stomach cardia cancer when CagA antibody shared negative but C-->T polymorphism occurred. CONCLUSION: C-->T polymorphism of iNOS gene was considered as one of the possible susceptible genes, which specifically increased the risk of tobacco-related but CagA negative types of intestinal stomach cancer and stomach cardia cancer.

Antibodies, Bacterial↗

PubMed2002

Polymorphisms in DNA repair genes and associations with cancer risk.

Common polymorphisms in DNA repair genes may alter protein function and an individual's capacity to repair damaged DNA; deficits in repair capacity may lead to genetic instability and carcinogenesis. To establish our overall understanding of possible in vivo relationships between DNA repair polymorphisms and the development of cancer, we performed a literature review of epidemiological studies that assessed associations between such polymorphisms and risk of cancer. Thirty studies of polymorphisms in OGG1, XRCC1, ERCC1, XPC, XPD, XPF, BRCA2, and XRCC3 were identified in the April 30, 2002 MEDLINE database (National Center for Biotechnology Information. PubMed Database: http://www.ncbi.nlm.nih.gov/entrez). These studies focused on adult glioma, bladder cancer, breast cancer, esophageal cancer, lung cancer, prostate cancer, skin cancer (melanoma and nonmelanoma), squamous cell carcinoma of the head and neck, and stomach cancer. We found that a small proportion of the published studies were large and population-based. Nonetheless, published data were consistent with associations between: (a) the OGG1 S326C variant and increased risk of various types of cancer; (b) the XRCC1 R194W variant and reduced risk of various types of cancer; and (c) the BRCA2 N372H variant and increased risk of breast cancer. Suggestive results were seen for polymorphisms in other genes; however, small sample sizes may have contributed to false-positive or false-negative findings. We conclude that large, well-designed studies of common polymorphisms in DNA repair genes are needed. Such studies may benefit from analysis of multiple genes or polymorphisms and from the consideration of relevant exposures that may influence the likelihood of cancer in the presence of reduced DNA repair capacity.

DNA Repair↗

PubMed2002

Gene polymorphisms of the renin-angiotensin-aldosterone system and essential arterial hypertension in childhood.

In order to investigate the contribution of candidate genes in the renin-angiotensin-aldosterone system (RAAS) in pathogenesis of essential arterial hypertension (EAH), the I/D polymorphism of ACE gene, the M235T polymorphism of the angiotensinogen gene, and the angiotensin II type 1 receptor (AGT,R) A1166C gene polymorphism in a group of children with EAH were analyzed. Fifty-scven children, aged 8-19 years. with the diagnosis of EAH were included in the association study and were compared with 57 subjects with normal blood pressure (the control group). Arterial hypertension was defined as systolic/diastolic blood pressure measurements higher than 95 age-gender-height percentile of the adopted reference values. A trend was found towards an association between the M235T angiotensinogen gene polymorphism and EAH in childhood in a dominant model (odds ratio (OR) 2.1; 95% confidence interval (CI) 0.9-5.1; P = 0.077), whereas the authors failed to demonstrate an association between the ACE I/D gene polymorphism, or the A1166C AGT1R gene polymorphism and EAH in childhood. Additionally, evidence was found of interaction between the angiotensinogen-TT genotype and obesity on the risk of EAH in childhood (OR 19.3; 95% CI 1.1-77.3; P = 0.014). In conclusion, the M235T angiotensinogen gene polymorphism is considered alone as well as in interaction with obesity to be risk factors for EAH in childhood.

Adolescent↗

PubMed2003

Analysis of the G/C polymorphism in the 5'-untranslated region of the RAD51 gene in breast cancer.

The breast cancer suppressor proteins BRCA1 and BRCA2 interact with RAD51, a protein essential for maintaining genomic stability by playing a central role in homology-dependent recombinational repair of the DNA double-strand breaks. Therefore, genetic variability in the RAD51 gene may contribute to the appearance and/or progression of breast cancer. A single nucleotide polymorphism in the 5'- untranslated region of RAD51 (a G to C substitution at position 135, the G/C polymorphism) is reported to modulate breast cancer risk. We investigated the distribution of genotypes and frequency of alleles of the G/C polymorphism in breast cancer. Tumor tissues were obtained from postmenopausal women with node-negative and node-positive breast carcinoma with uniform tumor size. Blood samples from age matched healthy women served as control. The G/C polymorphism was determined by PCR-based MvaI restriction fragment length polymorphism. The distribution of the genotypes of the G/C polymorphism did not differ significantly (P > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distribution and allele frequencies between node-positive and node-negative patients. There were no significant differences between distributions of the genotypes in subgroups assigned to histological grades according to Scarf-Bloom-Richardson criteria and the distribution predicted by Hardy-Weinberg equilibrium (P > 0.05). Our study implies that the G/C polymorphism of the RAD51 gene may not be directly involved in the development and/or progression of breast cancer and so it may not be useful as an independent marker in this disease.

5' Untranslated Regions↗

PubMed2003

Polymorphisms in the thymidylate synthase and methylenetetrahydrofolate reductase genes and sensitivity to the low-dose methotrexate therapy in patients with rheumatoid arthritis.

Methotrexate (MTX), widely used in the treatment of rheumatoid arthritis (RA), inhibits dihydrofolate reductase (DHFR) and folate-dependent enzymes. Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) are key enzymes in the folate metabolism and both have been shown to be polymorphic affecting the enzyme activity. To clarify the association between these genetic variations and MTX-related toxicity and efficacy in the treatment of RA, a total of 167 Japanese individuals with RA, including 52 and 63 patients treated with low-dose MTX with or without adverse effects, respectively, and 52 patients without MTX administration were analyzed. Among the 93 patients treated with MTX for >2 months, significantly more patients homozygous for the triple-repeat allele of the polymorphism in the promoter region of the TYMS gene required higher dose of MTX compared to those having at least a double-repeat allele (P=0.033). The incidence of > or =50% improvement in the serum CRP level was significantly higher in patients homozygous for the deletion allele of the polymorphism in the 3'-untranslated region (UTR) of the TYMS gene (P=0.0383). The allele frequency of the insertion/deletion polymorphism in the TYMS 3'UTR in Japanese was significantly different from that in Caucasians (P<0.0001), as was the tandem-repeat polymorphism in its promoter region. On the other hand, MTHFR C677T and A1298C polymorphisms showed no association with MTX-related toxicity or efficacy. Our results suggest that the genotyping for the TYMS polymorphisms may become a useful indicator in determining the appropriate dose of MTX in patients with RA.

Antirheumatic Agents↗

PubMed2003

Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk.

XRCC1 (X-ray cross-complementing group 1) and ERCC2 (excision repair cross-complementing group 2) are two major DNA repair proteins. Polymorphisms of these two genes have been associated with altered DNA repair capacity and cancer risk. We have described statistically significant interactions between the ERCC2 polymorphisms (Asp312Asn and Lys751Gln) and smoking in lung cancer risk. In this case-control study of 1091 Caucasian lung cancer patients and 1240 controls, we explored the gene-environment interactions between the XRCC1 Arg399Gln polymorphism, alone or in combination with the two ERCC2 polymorphisms, and cumulative smoking exposure in the development of lung cancer. The results were analyzed using logistic regression models, adjusting for relevant covariates. Overall, the adjusted odds ratio (OR) of XRCC1 Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was 1.3 [95% confidence interval (CI), 1.0-1.8]. Stratified analyses revealed that the ORs decreased as pack-years increased. For nonsmokers, the adjusted OR was 2.4 (95% CI, 1.2-5.0), whereas for heavy smokers (>/=55 pack-years), the OR decreased to 0.5 (95% CI, 0.3-1.0). When the three polymorphisms were evaluated together, the adjusted ORs of the extreme genotype combinations of variant alleles (individuals with 5 or 6 variant alleles) versus wild genotype (individuals with 0 variant alleles) were 5.2 (95% CI, 1.7-16.6) for nonsmokers and 0.3 (95% CI, 0.1-0.8) for heavy smokers, respectively. Similar gene-smoking interaction associations were found when pack-years of smoking (or smoking duration and smoking intensity) was fitted as a continuous variable. In conclusion, cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk.

Adult↗

PubMed2003

Study of the polymorphism of angiotensinogen, anigiotensin-converting enzyme and angiotensin receptor in type II diabetes with end-stage renal disease in Taiwan.

BACKGROUND: This study compared the polymorphisms of angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) gene between type II diabetes with diabetic nephropathy (DN) in end-stage renal disease (ESRD) and those of the normal individuals in Taiwan. METHODS: 129 patients with type II diabetes in ESRD from three dialysis centers were compared to 116 age and blood pressure-matched normal individuals. Polymerase chain reaction (PCR) specific for ACE gene was tested for insertion/deletion polymorphism. M235T and T174M variant polymorphisms of the AGT gene and the AT1R A1166C polymorphism were also tested according to previously described protocols. RESULTS: Between the two groups, frequencies of the alleles and the genotypes in ACE gene polymorphism were comparable. There was no significant difference of the ACE insertion and deletion polymorphism and AT1R gene polymorphism between the two groups. The allele frequencies of AGT point mutation at 235 (M235T) was significantly higher in DM nephropathy but the genotypic frequencies were not. In the AGT point mutation at 174 (T174M), the frequencies of both of alleles and genotypes were significantly higher in the DM nephropathy patients. CONCLUSIONS: In conclusion, there were significantly higher frequencies of alleles and genotypes in AGT point mutation at 174, which had never been reported before. In AGT point mutation at 235, there were significantly higher frequencies of alleles, but not genotypes in diabetic nephropathy. Our study suggested that the AGT gene plays an important role in diabetic nephropathy.

Adult↗

PubMed2003

Association between two polymorphisms in the SRD5A2 gene and serum androgen concentrations in British men.

Androgens are essential for the growth of the prostate gland and have been implicated in the development of prostate cancer. Little is known about the determinants of androgen levels in men, although observed ethnic differences suggest they may have a genetic basis. Several polymorphisms have been identified in the steroid 5 alpha-reductase type II gene (SRD5A2), which encodes an enzyme that catalyzes the conversion of testosterone to its more potent metabolite, dihydrotestosterone. Although some of these polymorphisms have been associated with increased prostate cancer risk, the association with circulating androgen levels remains unclear. The purpose of this study is to investigate the association between the (TA)(n) dinucleotide repeat polymorphism in the 3' untranslated region and the A49T polymorphism (which replaces the normal alanine with threonine at codon 49) in the SRD5A2 gene and serum androgen concentrations in 604 British men. In particular, we wanted to test the hypotheses that the variant alleles are associated with an increased serum concentration of androstanediol glucuronide, a direct metabolite of dihydrotestosterone and a serum marker of 5 alpha-reductase activity. Mean hormone concentrations were evaluated in each genotype, and adjusted for age and other relevant factors. We found no evidence that the SRD5A2 (TA)(n) repeat polymorphism was associated with androgen levels. Men who possessed one or two copies of the variant T allele in the A49T polymorphism had a significantly 24% lower androstanediol glucuronide concentration than men who were homozygous for the wild-type allele (P = 0.0003). Because of the rarity of this variant allele, larger studies are needed to additionally clarify the role of the A49T polymorphism in androgen metabolism.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2003

Polymorphism of alpha-estrogen receptor and aryl hydrocarbon receptor genes in dementia patients in Shanghai suburb.

AIM: To explore the possible association of different polymorphic forms of human alpha-estrogen receptor (ER-alpha) and aryl hydrocarbon receptor gene (Ahr) with the risk to senile dementia in farmers in Shanghai suburb. METHODS: Senile dementia patients (n=52) were examined for ER-alpha and Ahr gene polymorphism genotyping. Healthy individuals (n=125) in the same area were selected as a community control group. Two polymorphic loci, Pvu II locus and Xba I locus, of human ER- a gene were investigated by a PCR-RFLP-based procedure. The population frequencies of two polymorphic loci in exon 10 of Ahr gene, G1721A (R554K) and G1768A (V570I) were compared between patients and healthy controls using an allele-specific PCR (AS-PCR) procedure. RESULTS: The mutant allele frequencies of ER-alpha gene in the AD group were significantly higher than those in the control group (P=0.023, OR=2.94, 95 % CI 1.13-7.71 for Pvu II locus; P=0.046, OR=2.28, 95 % CI 1.003-5.17 for Xba I locus). The mutant allele frequencies among female AD patients were higher than those in the female controls (P=0.016, OR=3.68, 95 % CI 1.22-11.08 for Pvu II locus, P=0.029, OR=2.95, 95 % CI 1.10-7.94 for Xba I locus). The mutant form, neither in the homozygous, nor in the heterozygous form was detected at the locus of Ahr G1768A in a normal local population. No significant difference of Ahr genotype frequency at locus G1721A was noticed between the patients and healthy individuals. CONCLUSION: The distribution of ER polymorphisms was significantly different between Chinese and some other ethnic populations. The results suggested that ER-alpha gene polymorphisms might be related to the individual susceptibility to AD, especially in the females. However, it did not support the association of Ahr gene polymorphism with higher risk of senile dementia.

Aged↗

PubMed2003

[Analysis of glucocorticoid receptor gene polymorphisms by denaturing high-performance liquid chromatography].

OBJECTIVE: To detect polymorphisms of glucocorticoid receptor gene (NR3C1) in Chinese population with the technique of denaturing high-performance liquid chromatography (DHPLC). METHODS: Genomic DNA was isolated from peripheral blood of 2 healthy volunteer doctors and umbilical cord blood of 62 normal neonates. All the NR3C1-coding exons along with their flanking intron portions were amplified by polymerase chain reaction (PCR). For polymorphism screening, PCR products were analyzed by DHPLC. DNA fragments with aberrant elution profiles revealed by DHPLC were re-amplified and sequenced directly. RESULTS: Eight polymorphisms were identified by DHPLC and sequencing analysis. Among them, 5 (1374A > G, IVSG-68_IVSG-63delAAAAAA, 2193T > G, IVSH-9C > G, 2382C > T) were novel and 3 (1896C > T, 2166C > T, 2430T > C) were reported previously. Two groups of polymorphisms ([1374A > G + IVSG-68_IVSG-63delAAAAAA + IVSH-9C > G + 2382C > T] and [1896C > T + 2166C > T + 2430T > C]) showed to have the complete linkage disequilibrium and were identified as 2 different haplotypes, which was first reported. The frequencies of the 2 novel haplotypes were 3.1% and 14.1%, respectively. Another polymorphism (2193T > G) was relatively rare. CONCLUSION: DHPLC is a rapid and reliable method for polymorphism screening. Eight polymorphisms in the NR3C1 gene are detected in Chinese population with the technique of DHPLC, of which two haplotypes have been identified for the first time.

Asian People↗

PubMed1992

Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene are associated with changes in the concentration of apo B- and apo A-I-containing lipoproteins in a normal population.

The aims of this study were to detect polymorphic sites in the apolipoprotein (apo) A-IV gene, to establish their frequencies, to determine potential haplotypes, and to investigate the role of these polymorphisms in lipid metabolism. A sequencing study of four individuals led to the identification of two synonymous mutations (codons 9 and 54) and three nonsynonymous mutations (Val-8----Met, Gln360----His, and Thr347----Ser) and of a VNTR polymorphism within a series of three or four CTGT repeats in the noncoding region of exon 3. Frequencies of these polymorphisms were determined in 291 students by using naturally occurring (BstEII for the synonymous mutation in codon 54, HinfI for Thr347----Ser, and Fnu4HI for Gln360----His) or artificially introduced restriction-enzyme cutting sites (BstEII for the synonymous mutation in codon 9 and MamI for Val-8----Met), subsequent to PCR amplification. The four-base deletion/insertion polymorphism and its localization cis or trans to the mutations in codons 347 and 360 were studied by direct sequencing of PCR-amplified DNA from 87 students. Frequencies of the rarer alleles were .007 for apo A-IV-8:Met, .04 for the synonymous mutation in codon 9, .14 for the synonymous mutation in codon 54, .16 for apo A-IV347:Ser, .07 for apo A-IV360:His, and .39 for the four-base of insertion. Apo A-IV360:His in all cases was cis-localized to the (CTGT)3 repeat and apo A-IV347:Thr; and apo A-IV347:Ser was cis-localized to the (CTGT)4 repeat and apo A-IV360:Gln. Four haplotypes formed from these three polymorphic sites were thus found. The apo A-IV347:Ser allele was associated both with significantly lower plasma apo B concentrations in both sexes and with significantly lower LDL-cholesterol concentrations in men. Heterozygous carriers of apo A-IV360:His exhibited significantly higher concentrations of LDL-cholesterol and lower Lp(a) concentrations, compared with apo A-IV360:Gln homozygotes. We could not confirm the previously reported association of apo A-IV360:His with elevated HDL-cholesterol concentrations. In the population, the Val-8----Met polymorphism was not associated with significantly different lipid concentrations, but in a family study the Met-8 allele was associated with lower HDL-cholesterol and higher LDL-cholesterol concentrations. In conclusion, our results indicate an important role of the apo A-IV gene locus in the metabolism of apo B and, to a lesser extent, apo A-I containing lipoproteins.

Adult↗

PubMedDate not supplied

[Role of transforming growth factor beta-1 gene polymorphisms in the development of chronic allograft nephropathy in renal transplant recipients].

BACKGROUND: Chronic allograft nephropathy (CAN) is the main cause of graft loss after the first year of transplantation, and renal biopsies show a predominance of fibrotic lesions. Human transforming growth factor beta-1 (TGF-beta 1) is the principal profibrogenetic cytokine which has been recently implicated in the development of CAN. Seven TGF-beta 1 gene polymorphisms have been recently described and some of them have been related to the development of several diseases. AIM: To analyse the relationship between TGF-beta 1 gene polymorphisms and the development of CAN in a group of renal transplant patients with a long-term follow-up. METHODS: A restriction enzyme-based method for TGF-beta 1 genotyping was used to detect four TGF-beta 1 gene polymorphisms in codon 10, 25 and 5'-flanking region (-800 and -509 positions). A retrospective case-control study were performed on sixty renal transplant recipients with 8 years of post-transplant, 22 of them with CAN (cases) and 38 with normal graft function (controls). We studied 73 subjects to analyse the distribution of the genotypes in the area. RESULTS: The genotype frequencies were similar in the study and control group. The presence of chronic allograft nephropathy was statistically associated with the combination Pro/Pro10 TT509 polymorphism in the TGF-beta 1 gene, and these patients develop chronic rejection more quickly than the rest of the patients. Chronic allograft nephropathy was also associated with delta age recipient-donor, with older donors being a significant risk factor for chronic nephropathy. The logistic regression analysis confirmed the independent role of TT509 Pro/Pro10 TGF-beta 1 polymorphism with a Odd Ratio of 5.8 (1.14-29.7) in chronic nephropathy being the delta age recipient-donor a confounder factor but not an effect modifier. The rest of the TGF-beta 1 gene polymorphisms and the classic risk factors were not associated with the development of chronic allograft nephropathy. CONCLUSIONS: These data suggest a leading role for TGF-beta 1 gene polymorphisms (TT509 Pro/Pro10) in the development of chronic allograft nephropathy. The identification of this genetic predisposition to chronic allograft rejection could play a decisive role in the prevention of this common pathology.

Adolescent↗

PubMed2003

Association of an A allele for interleukin-10 -627 gene promoter polymorphism with higher susceptibility to endometriosis.

OBJECTIVE: To investigate whether interleukin-10 (IL-10) -627 gene promoter polymorphism could be used as a marker of susceptibility to endometriosis. STUDY DESIGN: Women were divided into 2 groups, endometriosis (n = 130) and nonendometriosis (n = 133). Polymorphisms for IL-10 -627 gene promoter were amplified by polymerase chain reaction and detected after restriction enzyme digestion. Genotypes and allelic frequencies in both groups were compared. RESULTS: Genotype proportions of different IL-10 gene polymorphisms in both groups were not significantly different. Proportions of A homozygote/heterozygote/T homozygote for IL-10 gene polymorphisms in both groups were 50%/40%/10% and 42.1%/38.4%/19.5%. In contrast, allele frequencies for IL-10 gene polymorphism between both groups were significantly different. Alleles A and C for IL-10 gene promoter polymorphism in the groups were 70%/30% and 61.3%/38.7%. A allele was associated with higher susceptibility to endometriosis. CONCLUSION: An association between endometriosis and IL-10 gene promoter polymorphism exists, and the IL-10 -627 A allele is related to a higher susceptibility to endometriosis.

Alleles↗

PubMed2003

IL-10 polymorphism is associated with increased incidence of severe sepsis.

OBJECTIVE: To investigate whether three biallelic polymorphisms at positions -592, -819 and -1082 in the promoter region of the IL-10 gene are associated with increased incidence of severe sepsis. METHODS: The IL-10 -592, -819 and -1082 polymorphisms were typed using polymerase chain reaction followed by digestion with the restriction enzymes RsaI, MaeIII and MnlI, respectively. RESULTS: Patients with severe sepsis were more likely to have IL-10 -1082 allele 1, compared with controls (P < 0.05). Genotype distribution of the IL-10 -1082 polymorphism significantly differed between patients and controls (P < 0.05). However, the allele frequencies and genotype distribution of the IL-10 -1082 polymorphism did not differ between surviving and dead patients (P > 0.05). No significant differences in the genotype distribution and allele frequencies of the IL-10 -592 and IL-10 -819 polymorphisms were observed between patients with severe sepsis and healthy controls, nor between surviving and dead patients (P > 0.05). CONCLUSIONS: The polymorphism at position -1082 in the promoter region of the IL-10 gene may be associated with susceptibility to severe sepsis. In contrast, the other two highly linked IL-10 polymorphisms are not associated with incidence or the outcome of severe sepsis.

Alleles↗

PubMed2004

Lack of association between endothelial nitric oxide synthase polymorphisms and Henoch-Schönlein purpura.

OBJECTIVE: To assess the influence of endothelial nitric oxide synthase (eNOS) polymorphisms in the susceptibility and clinical expression of patients with cutaneous vasculitis fulfilling classification criteria for Henoch-Schönlein purpura (HSP). METHODS: Fifty patients from Northwest Spain with primary cutaneous vasculitis classified as HSP were studied. Patients and ethnically matched controls (n = 117) were genotyped by polymerase chain reaction techniques for a variable-number tandem-repeat polymorphism in intron 4, a T/C polymorphism at position -786 in the promoter region, and a polymorphism in exon 7 (298Glu/Asp or 5557G/T) of the eNOS gene. RESULTS: No differences in allele or genotype frequencies for any of the individual eNOS polymorphisms were observed between patients fulfilling HSP classification criteria and controls, or when patients were stratified for the presence of nephritis or joint or gastrointestinal manifestations. In the HSP group no linkage disequilibrium between these polymorphisms was found. No significant difference in haplotype frequencies was observed between patients and controls. CONCLUSION: Our results do not support a role for these polymorphisms in the susceptibility to HSP.

Disease Susceptibility↗

PubMed2002

Frequencies of GSTM1, GSTT1, and GSTP1 polymorphisms in a Brazilian population.

The glutathione S-transferase (GST) family of enzymes has a vital role in phase II of biotransformation of environmental carcinogens, pollutants, drugs and other xenobiotics. GSTs are polymorphic, with the type and frequency of polymorphism being ethnic dependent. Polymorphisms in GST genes have been shown to be associated with susceptibility to disease and disease outcome. We determined the frequencies of GSTM1, GSTT1 and GSTP1 polymorphisms in 591 volunteers who had been residents of Rio de Janeiro for at least six months. Blood was collected and DNA extracted by proteinase K/SDS digestion. Information about social habits and health problems was also recorded. GSTM1 and GSTT1 polymorphisms were analyzed by a PCR-Multiplex procedure, whereas GSTP1 polymorphism was analyzed by PCR-RFLP. We found that 42.1% (48.9% of whites and 34.2% of non-whites) of the individuals had the GSTM1 null genotype, whereas 25.4% (25.1% of whites and 25.7% of non-whites) had the GSTT1 null genotype. The genotypic distribution of GSTP1 was 49.7% I/I, 38.1% I/V, and 12.2% V/V, whereas the allelic frequencies were 0.69 for the Ile allele, and 0.31 for the Val allele. The frequencies of GST polymorphisms in this Brazilian population were found to be different from those observed in other populations, particularly of other South American countries.

Adolescent↗

PubMed2003

PCR analysis of matrix metalloproteinase 3 (MMP-3) gene promoter polymorphism in ovarian cancer.

Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor-induced angiogenesis. The gene encoding MMP-3 is polymorphic and an insertion (6A)/deletion (5A) polymorphism (5A/6A polymorphism) in the MMP-3 gene may have functional significance in the regulation of its expression. In the present work the distribution of genotypes and frequency of alleles of the 5A/6A polymorphism in subjects with ovarian cancer were investigated. Paraffin embedded tumor tissues were obtained from 118 postmenopausal women with node-negative and node-positive ovarian cancer. The 5A/6A polymorphism was determined by PCR amplification using the allele specific primers. The distribution of the genotypes of the 5A/6A polymorphism in both control and study patients did not differ significantly (p>0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p>0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the 5A/6A polymorphism of MMP-3 gene may not be linked with appearance and/or progression of ovarian cancer.

Adenocarcinoma↗