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PubMed2001

Connexin37 gene polymorphism and coronary artery disease in Taiwan.

BACKGROUND: A recent study shows that a C1019T polymorphism of the gene encoding the gap junction protein connexin37 contributes to the genesis of atherosclerotic plaques in human carotid artery. However, whether such a polymorphism can be used as a prognostic marker in atherosclerotic disease of other arterial sites, such as coronary artery disease, is not known. METHODS: We analyzed the allelic status in 177 subjects with coronary artery disease (age, 61+/-11 years; male/female, 120/57) and 102 controls (60+/-11 years; male/female, 70/32). Both groups were matched, before genotype analysis, for a variety of other traditional risk factors, including body mass index, smoking status, levels of blood pressure, sugar, creatinine, and lipid profiles, in addition to age and sex. RESULTS: The T allele was less frequently seen in the control group, compared to the disease group (10.7 vs. 20.1%, TT+TC vs. CC, P<0.01). Subsequent analysis demonstrated that a significant difference existed in the male (9.2 vs. 22.8%, TT+TC vs. CC, P<0.005), but not in the female. Another finding was that the T allele frequency in all participants was less than 15%, markedly lower than that reported in non-Taiwanese. CONCLUSIONS: The observation indicates that the polymorphism in the connexin37 gene potentially plays a role in the manifestation of coronary atherosclerosis in Taiwan.

Aged↗
PubMed2004

Leukotriene-related gene polymorphisms in ASA-intolerant asthma: an association with a haplotype of 5-lipoxygenase.

A recent study has demonstrated the possible involvement of a leukotriene C4 synthase (LTC4S) gene polymorphism in ASA-intolerant asthma (AIA) in a Polish population, whereas no significant association was noted in other populations. To investigate the role of genetic polymorphism in AIA development, we screened single nucleotide polymorphisms (SNPs) of the key enzymes involved in arachidonate metabolism, and the cysteinyl leukotriene receptor 1 (CYSLTR1) in a large Korean population with AIA: 93 AIA and 181 ASA-tolerant asthma (ATA) patients, and 123 normal controls. The single-base extension method was used to genotype SNPs in 5-lipoxygenase (ALOX5, -1708G-->A, 21C-->T, 270G-->A, 1728G-->A), ALOX5-activating protein (ALOX5AP, 218A-->G), prostaglandin-endoperoxide synthase 2 (PTGS2, COX2, -162C-->G, 10T-->G, R228H, V511A), LTC4S (-444A-->C), and CYSLTR1 (927T-->C). Haplotype analyses were undertaken for the SNPs in ALOX5. No significant differences in allele and genotype frequencies of single SNPs were observed between the patient groups ( P>0.05). However, the frequency of the ALOX5-ht1[G-C-G-A] haplotype in the AIA group was significantly higher than its frequency in the ATA group with a probability ( P) of 0.01, odds ratio (OR) of 5.0, and 95% confidence interval (95%CI) of 1.54-17.9, and in the normal controls ( P=0.03, OR=4.5, 95%CI=1.1-18.4), by using a dominant model. These results suggest a lack of association between the ALOX5AP, PTGS2, LTC4S, and CYSLTR1 gene polymorphisms and the AIA phenotype in the Korean population. However, the possible involvement of ALOX5-ht1[G-C-G-A] in AIA development is suggested.

5-Lipoxygenase-Activating Proteins↗
PubMed2006

Phenotypic variation in constitutional delay of growth and puberty: relationship to specific leptin and leptin receptor gene polymorphisms.

OBJECTIVES: Constitutional delay of growth and puberty (CDGP) is a variant of normal pubertal timing and progress, often with dominant inheritance. It is likely that one or more genes will be associated with CDGP. Possible candidates are the leptin (L) and the leptin receptor (LR) genes, as the leptin axis links nutritional status to pubertal development. This study has assessed whether a) L or LR gene polymorphisms were associated with CDGP and b) the CDGP phenotype was influenced by these polymorphisms. DESIGN: Case-control and transmission disequilibrium tests were used to test genetic association of L and LR polymorphisms with CDGP. METHODS: We genotyped L (3'CTTT repeat) and LR polymorphisms (Gln > Arg substitution, exon 6) in 81 CDGP children and 94 controls in the UK and 88 CDGP children from the US and assessed the effect of genotype on their anthropometric characteristics. RESULTS: There was no association of these L or LR gene polymorphisms with CDGP. There was no difference in height or bone age delay within L or LR genotypes. However, UK CDGP children homozygous for the L short allele were heavier than heterozygotes and long allele homozygotes, with a similar trend in the US cohort. UK CDGP children with severe pubertal delay, who were thin, had significantly greater bone age delay and an increased frequency of parental pubertal delay than other groups and were less likely to be L short allele homozygotes. CONCLUSIONS: There was no association of specific L or LR polymorphisms with CDGP, but L short allele carriage influenced the phenotype within CDGP.

Adolescent↗
PubMed2006

Association study between catalase gene polymorphisms and the susceptibility to vitiligo in Korean population.

Vitiligo is an acquired pigmentary disorder characterized by well-circumscribed depigmented patches. Autoimmune, self-destruction, neural, and genetic theories have been proposed for the pathogenesis of vitiligo. Reactive oxygen species play an important role in the physiology of cell damage, and catalase is known to regulate oxidative stress. Reduced catalase enzyme activity and accumulation of excessive hydrogen peroxide were observed in vitiligo. To examine whether catalase gene polymorphisms are associated with vitiligo patients in Korean population, we investigated two CAT gene polymorphisms including (T/C) BstX I (A/T) Hinf I in 118 vitiligo patients and 200 healthy volunteers. The CAT gene genotype distribution and allele frequency were not significantly different between vitiligo patients and healthy controls. But, the haplotype of two polymorphisms was associated with vitiligo. This study suggests possible association between the CAT gene and the vitiligo susceptibility.

Adult↗
PubMed2004

Osteoprotegerin gene polymorphisms in men with coronary artery disease.

Osteoprotegerin (OPG) antagonizes receptor activator of nuclear factor-kappaB ligand (RANKL), the principal regulator of osteoclasts. Of note, OPG-deficient mice display osteoporosis and arterial calcification. Recently, OPG gene polymorphisms have been associated with osteoporosis and early predictors of cardiovascular disease. In this study, we examined OPG gene polymorphisms in 468 men who had absence of coronary artery disease (CAD) or single-, double-, or triple-vessel disease on coronary angiography. Denaturing gradient gel electrophoresis followed by DNA sequencing revealed nucleotide substitutions 149 T-->C, 163 A-->G, 209 G-->A, 245 T-->G, 950 T-->C (all promoter), 1181 G-->C (exon 1), and 6890 A-->C (intron 4), respectively. Although single polymorphisms were not associated with CAD, linkage of polymorphisms 950 and 1181 revealed that haplotypes were overrepresented in men with CAD (chi(2) = 17.05; P = 0.03) with an increased risk of CAD in carriers of genotypes 950 TC/1181 GC and 950 CC/1181 CC (odds ratio, 1.67; 95% confidence interval, 1.02-2.72; P = 0.04). Furthermore, serum OPG levels were correlated with the presence of a C allele at position 950 (P = 0.02). In summary, linkage of genetic variations of the OPG gene at positions 950 and 1181 may confer an increased risk of CAD in Caucasian men.

Alleles↗
PubMed2006

[Serotonin transporter gene polymorphism in slow transit constipation].

OBJECTIVE: To investigate the association between the polymorphism of serotonin transporter gene-linked polymorphic region(5-HTTLPR) and slow transit constipation(STC). METHODS: Polymerase chain reaction was used to assess 5-HTTLPR polymorphism of SERT gene in 54 patients with STC and 100 healthy controls. RESULTS: The frequencies of serotonin transporter short/short(S/S) and allele S genotypes were significantly higher in STC patients than those in controls(72.2% vs 50.0%; 83.3% vs 72.5%; both P< 0.05). There were no significant differences in 5-HTTLPR polymorphism respectively between the two groups according to gender and age(less than 45 and more than 45 years old). The frequency of S/S genotype was higher in the patients with less than 40% of the ingested markers evacuated within 72 h than those with more than 40% evacuated(71.7% vs 42.6%, P< 0.05). CONCLUSION: The presence of 5-HTTLPR allele S may contribute to the pathogenesis of STC.

Adolescent↗
PubMed2001

Paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level as possible risk factors for exudative age-related macular degeneration.

PURPOSE: Paraoxonase (E.C.3.1.1.2) is a polymorphic protein shown to prevent low-density lipoprotein oxidation. Our purpose is to evaluate the hypothesis that paraoxonase gene polymorphisms and plasma oxidized low-density lipoprotein level play a role in the occurrence of exudative age-related macular degeneration. METHODS: We analyzed paraoxonase genotypes (A/B, Gln-Arg192 and L/M, Leu-Met54) and plasma oxidized low-density lipoprotein levels in 72 unrelated Japanese patients with exudative age-related macular degeneration and compared the results with those of 140 age-matched and sex-matched control subjects. RESULTS: The distribution of paraoxonase 192 and paraoxonase 54 polymorphisms was significantly different between the patients with age-related macular degeneration and control subjects (chi-square = 6.226, P =.0445, and chi-square = 6.863, P =.0323, respectively). The high frequency of the BB genotype at position 192 was observed in the exudative age-related macular degeneration group compared with control subjects (52.8% vs 35.0%, respectively; P =.0127). The high frequency of the LL genotype at position 54 was observed in the patients more than the controls (91.7% vs 77.1%, respectively; P =.0090). The mean (+/- SE) oxidized low-density lipoprotein levels in the patients was significantly higher than in the controls (19.1 +/- 1.0 vs 16.2 +/- 0.6 U/ml, P <.01). CONCLUSION: These results indicate that the paraoxonase gene polymorphisms may represent a possible genetic risk factor for age-related macular degeneration and that increased plasma oxidized low-density lipoprotein may be involved in the pathogenesis of age-related macular degeneration.

Aged↗
PubMedDate not supplied

TNF-alpha promoter gene polymorphisms in Spanish children with persistent oligoarticular and systemic-onset juvenile idiopathic arthritis.

OBJECTIVE: To explore the possible association/s of the first reported tumour necrosis factor (TNF-alphaTNF-) alpha promoter gene polymorphisms -308, -238, -376 and -163 (G-->A) with systemic (SoJIA) and oligoarticular subtypes of juvenile idiopathic arthritis (JIA); and to test the association between these polymorphisms and the class I/class II HLA alleles in our population. METHODS: The patient group comprised 29 oligoarticular and 26 systemic Caucasian Spanish children with JIA; 68 healthy volunteers from the same ethnic group and geographical region served as controls. HLA alleles were determined using low-resolution polymerase chain reaction (PCR). TNF-alpha promoter gene polymorphisms were screened using PCR denaturing gradient gel electrophoresis (PCR-DGGE), followed, if positive, by restriction fragment length polymorphism (RFLP) analysis for identification. RESULTS: No statistical association was found between the four polymorphisms studied and JIA. However, the -308 G-->A polymorphism (TNF A2) tended to be more frequent in patients with SoJIA than in the oligoarticular group. TNF A2 was strongly associated with the extended haplotype A1B8DR3 (p = 0.003), and the tandem polymorphism -238/-376 in the presence of B18 and DR3. CONCLUSION: The TNF A2 allele was more frequent in SoJIA than in the oligoarticular group. TNF A2 can help to create a more inflammatory milieu in this JIA subtype, in combination with other polymorphisms involved in regulatory sequences of key molecules in the inflammatory response. The association of the -308 and -238/-376 polymorphisms with specific alleles of the HLA is reconfirmed.

Arthritis, Juvenile↗
PubMed2005

[The relationship between methylenetetrahydrofolate reductase gene polymorphism and microsatellite instability in gastric cancer].

OBJECTIVE: To explore the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and microsatellite instability (MSI) in patients with gastric cancer. METHODS: MTHFR gene C677T and A1298C polymorphism were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and MSI was examined with PCR. RESULTS: MTHFR gene C677T and A1298C polymorphisms were analyzed on 122 gastric cancers and 110 normal controls The genotype frequencies of MTHFR 677CC, 677CT and 677TT were 47.5%, 39.3% and 13.1% on patients with gastric cancer, and 48.5%, 42.6%, 8.9% in the controls respectively. There was no significant difference of genotype frequency between the two groups (P > 0.05). The individuals with 677CT genotype, 677TT genotype and 677CT + TT genotype exhibited significantly reduced risk (OR = 0.38,95% CI: 0.15-0.98; OR = 0.26,95% CI: 0.03-2.18 and OR = 0.36,95% CI: 0.07-0.98) of developing gastric cardia cancer compared with those harboring the wild-type(677CC). The individuals with 677TT genotype having a 3.03-fold (95% CI: 1.07-8.65) increased risk of developing gastric corpus cancer. The genotype frequency of MTHFR 1298AA, 1298AC and 1298CC were 59.8%, 36.1% and 4.1% in gastric cancer patients, and 57.4%, 7.6%, 5.0% in the controls, respectively. The distribution of MTHFR A1298C genotype was not significantly different between gastric cancer and controls (P > 0.05). The individuals with 1298CC genotype had a reduced risk of developing gastric antrum cancer (OR = 0.41- fold, 95% CI: 0.03-2.18, 0.05-3.72) when comparing with those having 1298AA genotype. Patients with MSI+ gastric cancer had an increased frequency of the MTHFR 677TT genotype when comparing with those suffering from MSI- gastric cancer (P = 0.009) and with controlled subjects (P = 0.008). There was no significant association found between MTHFR A1298C polymorphism and MSI (P>0.05). CONCLUSION: Polymorphism of MTHFR C677T was associated with increased risk on gastric corpus cancer and reduced risk on gastric cardia cancer. The polymorphism of MTHFR A1298C was associated with reduced risk for gastric antrum cancer while MSI pathway was possibly involved in the development of gastric cancer with MTHFR 677TT genotype.

Adult↗
PubMed2006

CYP1A1 gene polymorphism as a risk factor for cervical intraepithelial neoplasia and invasive cervical cancer.

OBJECTIVE: The purpose of this study was to evaluate the role of CYP1A1*3 gene polymorphism in the development of cervical cancer by comparing patients having cervical intraepithelial neoplasia (CIN) or invasive cervical cancer with control subjects. METHODS: CYP1A1*3 polymorphism was analyzed using an allele-specific PCR-based method. RESULTS: In the group of patients with CIN, the frequency of the Ile/Val and of any Val alleles was significantly higher than in the healthy control subjects (OR: 4.51; 95%CI = 2.42-8.43, and OR: 3.71; 95%CI = 2.03-6.78). In the CIN1 group, patients with Ile/Val and any Val genotypes were found to be significantly higher (OR: 10.53; 95%CI = 3.78-29.33 and OR: 8.38; 95%CI = 3.04-23.08). In the CIN2 group, patients with Ile/Val and any Val revealed a 4.06- and 3.23-fold higher risk than those with Ile/Ile (95%CI = 1.54-10.74 and 1.24-8.45). However, the variance in the group of patients with CIN3 did not reach statistical significance. Patients with cervical cancer were analyzed with respect to the histological diagnoses. In the adenocancer group, the estimated ORs with respect to the control subjects were 11.29 for Ile/Val (95%CI = 3.35-38.07) and 8.98 for any Val groups (95%CI = 2.69-30.01), with a statistical significance. Among the squamous cell cancer patients, Ile/Val and any Val were significantly higher than in controls (OR: 5.76; 95%CI = 3.13-10.59 and OR: 5.20; 95%CI = 2.91-9.28). Although Val/Val genotype did not reach a significant value, it was near significance with an OR of 3.03 (95%CI = 0.95-9.68). CONCLUSION: These results suggest that CYP1A1*3 gene polymorphism is linked to a propensity for cervical carcinogenesis and further series are needed to detect the exact role of this unique variation.

Adult↗
PubMed2005

DNA repair gene polymorphisms in relation to chromosome aberration frequencies in retired radiation workers.

Polymorphic variation in DNA repair genes was examined in a group of retired workers from the British Nuclear Fuels plc facility at Sellafield in relation to previously determined translocation frequencies in peripheral blood lymphocytes. Variation at seven polymorphisms in four genes involved in the base excision repair (XRCC1 R194W, R399Q and a [AC]n microsatellite in the 3' UTR) and double strand break repair (XRCC3 T241M and a [AC]n microsatellite in intron 3 of XRCC3, XRCC4 I134T, and a GACTAn microsatellite located 120 kb 5' of XRCC5) pathways was determined for 291 retired radiation workers who had received cumulative occupational external radiation doses of between 0 and 1873 mSv. When the interaction between radiation dose and each DNA repair gene polymorphism was examined in relation to translocation frequency there was no evidence for any of the polymorphisms studied influencing the response to occupational exposure. A positive interaction observed between genotype (individuals with at least one allele > or =20 repeat units) at a microsatellite locus in the XRCC3 gene and smoking status should be interpreted cautiously because interactions were investigated for seven polymorphisms and two exposures. Nonetheless, further research is warranted to examine whether this DNA repair gene variant might be associated with a sub-optimal repair response to smoking-induced DNA damage and hence an increased frequency of translocations.

Aged↗
PubMedDate not supplied

Relationship of osteocalcin and matrix Gla protein gene polymorphisms to serum osteocalcin levels and bone mineral density in postmenopausal Korean women.

OBJECTIVE: To investigate the relationship of osteocalcin and matrix Gla protein (MGP) gene polymorphisms to serum osteocalcin levels, and bone mineral density (BMD) in postmenopausal Korean women. DESIGN: The osteocalcin gene Hind III and MGP gene cytosine-adenine polymorphisms were analyzed in 267 postmenopausal Korean women. Serum osteocalcin, bone alkaline phosphatase, C-telopeptide of type I collagen, and BMD at the lumbar spine and femoral neck were measured. RESULTS: No significant differences in BMD of the lumbar spine and femoral neck were observed across MGP genotypes, whereas a significant lower BMD at the lumbar spine (but not at the femoral neck) was observed in women with the (h) allele (lower case 'h' signifies the presence of the Hind III site) in a dose-response manner. Serum osteocalcin levels among bone turnover markers studied were significantly higher in women without the 210-bp MGP (cytosine-adenine) allele, or with the osteocalcin hh genotype. CONCLUSIONS: The osteocalcin gene Hind III polymorphism is a genetic factor that is associated with BMD of the lumbar spine in Korean women, and Gla gene polymorphisms are associated with higher osteocalcin levels.

Aged↗
PubMed2002

MICA gene polymorphisms in an Italian paediatric series of juvenile Behçet disease.

The objective of this study was to investigate MICA (major histocompatibility complex MHC class I chain-related genes) polymorphisms in an Italian series of patients with juvenile Behcet disease (jBD) and to compare these genetic findings with the high prevalence of inflammatory mucosal disease, which occurs in Western populations. Ten families which included at least 1 affected patient were studied. We genotyped 18 patients (13 children and 5 adults) affected with the complete or incomplete form of jBD comparing the results to those found in a population of 20 apparently healthy individuals. The MICA transmembrane polymorphism was analysed by PCR and polyacrylamide gel electrophoresis. HLA typing was assessed by SSP-PCR technique. Statistical analysis was performed using chi2 based methods. In our series the prevalence of gastrointestinal disease was high (41%). Seven of 10 patients were HLA-B51 positive. MICA A6 allele was present in 70% of probands as compared to 25% of an ethnically matched control population. On the other hand, MICA A5.1 was present in 20% of probands as compared to 60% in controls. Out of 5 A6 homozygotes, 2 probands and 2 affected relatives developed a severe gut inflammatory disease. The study of MICA gene polymorphisms disclosed an independent association with genetic risk for jBD. The combination of MICA A6 and HLA-B51 is the strongest genetic marker for this disease. Homozygous A6 patients seem to develop more severe mucosal gut involvement. This finding sheds light on the role of a receptor for MICA, named NKG2D, presented by natural killer cells, and CD8+, alphabetaT cells and gammadeltaT cells, usually localised in gut mucosa.

Adult↗
PubMed2006

Lack of association between the platelet glycoprotein Ia C807T gene polymorphism and coronary artery disease: a meta-analysis.

BACKGROUND: The platelet-collagen receptor, glycoprotein (GP) la/lla plays a crucial role in the adhesion of platelets to fibrillar collagen, an event contributing to the pathogenesis of thrombosis. The C807T polymorphism of the GPla gene is considered a genetic marker of the platelet GPla/lla density. The importance of the GPla gene C807T polymorphism as a genetic risk factor for coronary artery disease (CAD) remains controversial. To assess this association, we performed a meta-analysis of published data. METHODS: A comprehensive meta-analysis of 19 studies, with a total sample of 13835 subjects using random effects models. RESULTS: The C versus T allele contrast gave an OR of 0.998 with 95% Cl 0.937-1.064. Similarly, comparing the C homozygotes with the T homozygotes, the CC genotype versus the others and the TT genotype versus the rest, no evidence of any gene-disease association was obtained. Furthermore, the meta-regression analysis did not disclose any variable that could modify the role of this polymorphism in the development of CAD. CONCLUSION: Our findings support the view that C807T polymorphism of the GPla gene is not a significant risk factor for CAD, either alone or in combination with other major cardiovascular risk factors.

Coronary Artery Disease↗
PubMed2004

Estrogen receptor alpha gene polymorphisms and bone mineral density in healthy children and young adults.

The accretion of peak bone mass is largely under genetic control, and one of the potential candidate genes is the estrogen receptor alpha (ERalpha) gene. The association of ERalpha gene polymorphisms with bone mineral density (BMD) was investigated in a group of 147 healthy caucasian children, adolescents, and young adults (57 boys and 90 girls) in a cross-sectional and longitudinal study. The mean age was 11.3 years (4.3-19.9 years) at baseline and 15.6 years (7.6-25.3 years) at follow-up. Lumbar spine, total body BMD, and body composition were measured by dual energy X-ray absorptiometry and expressed as age- and sex-adjusted standard deviation scores (SDS). We analyzed two restriction fragment length polymorphisms, Pvull and Xbal, and haplotypes thereof. Subjects homozygous for haplotype 1 (px) (33% of the population) had 0.4 SD (standard deviation) lower lumbar spine BMD (P = 0.02) and bone mineral apparent density (BMAD) (P = 0.04) than those heterozygous or noncarriers for haplotype 1 (px) at baseline. Analysis of the follow-up data gave similar results. The association was stronger for the prepubertal than for the postpubertal subjects. Vertebral width SDS, total body BMD SDS, height SDS, body mass index SDS, lean body mass SDS, and percentage fat SDS did not significantly differ between the haplotypes. The age of menarche was not related to any of the haplotypes in girls. The present study shows that Pvull-Xbal ERalpha gene polymorphism is associated with BMD during childhood.

Absorptiometry, Photon↗
PubMed2005

[Relationship between GSTM1 and GSTT1 gene polymorphisms and noise induced hearing loss in Chinese workers].

OBJECTIVE: To investigate the relationship of GSTM1 and GSTT1 gene polymorphisms with the development of noise induced hearing loss (NIHL) in Chinese workers. METHODS: 194 workers exposed to occupational noise were drawn as the subjects in the cross-sectional epidemiological study. According to the result of audiometry, they were divided into two groups: the NIHL group and the normal group. The GSTM1 and GSTT1 genotypes of 93 workers with NIHL and 101 normal workers were tested by multiplex polymerase chain reaction. Results The study showed that there were no significant differences in the distribution of GSTM1 and GST1 existed/null genotypes frequencies between NIHL group and normal group (P > 0.05). After adjusted for age, sex, smoking, history of explosive noise exposure and cumulative noise exposure (CNE) with multiple logistic regression analysis, the risk of GSTT1 null group was found significantly higher than that of the GSTT1 non-null group (P < 0.05), the adjusted OR value of which was 1.952 (95% confidence interval 1.017 - 3.746). There was no significant difference between the GSTM1 null group and the GSTM1 non-null group in the risk of NIHL (P > 0.05). CONCLUSION: The results suggested that genetic polymorphism in GSTTI1 gene might play an important role in the development of NIHL in Chinese workers; the individuals with the GSTT1 null genotype might be more susceptible to NIHL.

Adult↗
PubMed2005

Lack of association between antioxidant gene polymorphisms and progressive massive fibrosis in coal miners.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of interstitial lung diseases. The antioxidant enzymes glutathione S-transferases (GST) and manganese superoxide dismutase (MnSOD) are important components of lung defence against oxidative stress, and polymorphisms in the genes which regulate their expression may represent important disease modifiers. METHODS: A matched case-control study was conducted to determine the influence of the GSTP1, GSTT1 and MnSOD polymorphisms on susceptibility to progressive massive fibrosis (PMF). Seven hundred ex-coal miners were included in the study; 350 were classified as PMF cases while 350 with a similar underground mining tenure but no clinical or histological evidence of lung disease served as controls. Genotype analysis was performed on genomic DNA, using a 5' nuclease PCR assay. RESULTS: None of the individual investigated polymorphisms and two-way gene-gene interactions had a statistically significant association with PMF. CONCLUSION: The results of this study suggest that polymorphic genotypes within the GST gene cluster and MnSOD do not affect individual susceptibility to PMF.

Aged↗
PubMed2004

Association of plasminogen activator inhibitor-1 4G/5G gene polymorphism with variations in the LDL particle size in healthy Japanese men.

BACKGROUND: Several studies have supported the association between a predominance of small, dense low-density lipoprotein (LDL) and the risk of coronary artery disease. As another potentially atherogenic factor, impaired fibrinolytic activity due to increased plasminogen activator inhibitor-1 (PAI-1) concentrations has been shown. In addition, the 4G allele of the 4G/5G polymorphism in the promoter region of the PAI-1 gene is reported to be associated with the atherogenic lipid profile. We investigated the relation between the PAI-1 gene polymorphism and LDL particle size. METHODS: A total of 156 healthy Japanese male subjects were recruited. The diameter of LDL particles was determined at their peak size using polyacrylamide gels using fresh plasma samples. RESULTS: Fasting insulin and triglyceride concentrations were found to be significantly higher, and the LDL particle size was smaller in the homozygotes for the 5G allele than in the carriers of the 4G allele. An analysis of covariance (ANCOVA) adjusting for insulin and triglyceride concentrations showed a consistently significant difference in LDL particle size between the two groups. In the forward stepwise multiple regression analysis, triglycerides, insulin, and the PAI-1 5G/5G genotype remained in the model as independent and significant predictors capable of influencing the LDL particle size. CONCLUSIONS: Our findings suggest that the 4G/5G polymorphism of the PAI-1 gene might be associated with LDL particle size in healthy Japanese males.

Adult↗