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PubMed2005

[G691S, L769L and S836S ret proto-oncogene polymorphisms are not associated with higher risk to sporadic medullary thyroid carcinoma in Chilean patients].

BACKGROUND: Medullary thyroid carcinoma (MTC) may occur either as sporadic or as hereditary. Even though the sporadic form corresponds to the majority of cases, the pathogenesis is still unclear. Several polymorphisms of the ret proto-oncogene, including those located in exon 11, 13, 14 and 15 have been described in the general population and some of them seem to be over-represented in sporadic MTC patients from European countries, especially G691S, L769L and S836S. AIM: To evaluate the allele frequencies of these variants in Chilean patients and controls and to determine if these polymorphisms would be associated with the development of sporadic MTC from a different genetic population base. SUBJECTS AND METHODS: Fifty sporadic MTC patients and 50 normal subjects were tested for G691S, L769L, S836S and S904S polymorphisms. The extracted genomic DNA was initially analyzed by direct sequencing of PCR products in patients. The presence or absence of each polymorphism was also assessed in patients and in control by restriction digestion. RESULTS: The allele frequencies showed a similar level of the G691S, L769L and S904S variants in both groups. Of interest, we found an under-representation of S836S polymorphism in the sporadic MTC group but this number was not statistically significant (p=0.141). CONCLUSIONS: We did not find an over representation of the G691S, L769 and S836S. These results argue against the validity of the association of these polymorphisms as contributing factors in the development of sporadic MTC based on a Chilean population and raise questions about the importance of these polymorphisms overall.

Carcinoma, Medullary↗

PubMed2002

Factor XIII polymorphisms and venous thromboembolism.

OBJECTIVE: To review the relationship between factor XIII polymorphisms and venous thromboembolism. METHODS: Review of the medical literature using computerized databases and secondary sources identified through reviews of bibliographies. DATA SYNTHESIS: Plasma factor XIII is the precursor of a transglutaminase that cross-links fibrin, thereby altering its properties, including resistance to fibrinolysis. It is, therefore, biologically plausible that alterations in factor XIII activity could affect thrombosis risk. There are 4 common polymorphic forms of factor XIII that differ among ethnic groups. The Val34Leu polymorphism results in an amino acid change near the thrombin cleavage site that may alter the rate of activation. Several case-control studies have investigated the relation of the Val34Leu polymorphism to venous thromboembolism. Some have shown a potentially protective effect of this polymorphism, but the association is not consistent. CONCLUSION: Evidence is conflicting regarding the association of the factor XIII Val34Leu polymorphism with risk of venous thromboembolism, and further studies are needed before screening for this polymorphism can be recommended for evaluation of thrombophilia.

Blood Coagulation Tests↗

PubMed1999

[Genetic linkage of polymorphisms of type I angiotensin II receptor gene to Chinese Han hypertension].

OBJECTIVE: To observe the CA repeat polymorphism of the type I angiotensin II receptor gene on Chinese Han people, and evaluate the genetic linking to hypertension. METHODS: The CA repeat polymorphism at 3'-flanking region of AT1R gene was studied by amplified fragment length polymorphism (Amp-FLP ) in Chinese Han people from Shandong and Xi'an. RESULTS: There were 9 alleles ranging from 130bp to 146bp in all subjects. The allele frequencies were 0.01 to 0.38, and allele A4 was more frequent in the control. The heterozygosity of CA repeat locus was 0.789, the polymorphic information content, 0.746. There was no significant difference in distribution of CA repeat polymorphism genotype between different regions in same ethnic (P>0. 05), but the allele frequency of CA repeat polymorphism in hypertensive group was significantly different from that of control (P<0.05). There was no detectable distortion from Hardy-Weinberg equilibrium in both groups. CONCLUSION: The results suggest that CA repeat polymorphism of AT1R gene be associated with Chinese Han hypertensive people.

Adult↗

PubMed1999

A novel polymorphism (-357 G/A) of the ALDH2 gene: linkage disequilibrium and an association with alcoholism.

BACKGROUND: Human mitochondrial aldehyde dehydrogenase (ALDH2) is a major enzyme responsible for the oxidation of acetaldehyde derived from ethanol metabolism. The human ALDH2 gene shows genetic polymorphism at position 1510 with a G to A transition in exon 12. This mutation leads to ALDH2 enzyme deficiency and protection against alcoholism. As yet, no polymorphism for the promoter region of the ALDH2 gene has been reported. METHODS: We analyzed 600 nucleotides of the promoter region in addition to exon 12 from 571 Japanese, 68 Chinese, 80 Myanmar, 60 Mongolians, and 82 North-American Caucasians using single-strand conformational change polymorphism (SSCP) analysis and the polymerase chain reaction (PCR). PCR products that showed an aberrant banding pattern detected by the SSCP analysis were subjected to PCR direct sequencing. RESULTS: A novel polymorphism at -357 with a G to A substitution was found in all the population groups, including North-American Caucasians. In addition, the polymorphic status in the promoter and exon 12 suggested linkage disequilibrium between the two loci, which indicated that among Japanese, the ALDH2*2 allele is linked to the G promoter allele, and theALDH2*1 allele is linked to the A allele. A total of 206 healthy male controls and 185 alcoholic male patients with the homozygous ALDH2*1 genotype were analyzed for the polymorphism in the promoter. Genotypic frequencies of GG, GA, and AA for alcoholics were 54.1%, 44.3%, and 1.6%, and those for controls were 52.9%, 40.3%, and 6.8%, respectively. The A allele frequencies for alcoholics and controls were 0.24 and 0.27, respectively. A chi2 test for the entire 3 x 2 table indicated significant variations in the three genotypes (chi2 = 6.40, p < 0.05). However, no significant difference in allelic frequencies between the two groups was observed. CONCLUSION: This new polymorphism in the ALDH2 promoter is present in all populations studied. Further analysis in other ethnic groups is necessary to establish this as an additional risk factor for alcoholism.

Adult↗

PubMed1999

An A/G polymorphism in the promoter of mitochondrial aldehyde dehydrogenase (ALDH2): effects of the sequence variant on transcription factor binding and promoter strength.

INTRODUCTION: The strong protective effect of the ALDH2*2 mutation on risk of alcoholism suggests that other mutations that reduce mitochondrial aldehyde dehydrogenase (ALDH) activity in the liver might also deter drinking. This study describes a polymorphic locus found in the promoter of the ALDH2 gene that affects expression of reporter constructs. METHODS: Polymerase chain reaction (PCR)-based sequencing was used to search for polymorphisms. The ability of the promoter variants to bind transcription factors apolipoprotein A regulatory protein 1 (ARP-1) and chicken ovalbumin upstream promoter-transcription factor (COUP-TF) was tested in gel retardation assays using in vitro synthesized transcription factors. The variant promoters were tested for transcriptional activity using a heterologous promoter system and transient transfection assays. RESULTS: A common polymorphism (A or G) in the human ALDH2 promoter region was found at -361 base pair (bp) from the translation start site. This polymorphism was found at different frequencies in African Americans, Caucasians, and Asians. The polymorphism occurs adjacent to the core binding motif for the transcription factors COUP-TF and ARP-1. Competition and binding affinity determinations did not show differences in the ability of these two sequences to bind the factors. Reporter genes containing these elements upstream of a basal thymidine kinase promoter had similar activity when transfected into a fibroblast (CV-1) cell line. However, the reporter containing the G allele was more active than that containing the A allele in hepatoma (H4IIEC3) cells. CONCLUSIONS: The -361 bp A/G polymorphism is common in all racial groups tested. The G allele was more active than the A allele in a transfection assay. The basis for this difference is not known. If the differences in activity of the promoter constructs were paralleled by differences in ALDH2 enzyme activity in the liver, this polymorphism could affect risk of alcoholism.

Aldehyde Dehydrogenase↗

PubMed1999

Polymorphisms of platelet membrane glycoprotein Ib alpha and plasma von Willebrand factor antigen in coronary artery disease.

To examine the relationships of two polymorphisms of platelet glycoprotein (GP) Ib alpha and coronary artery diseases (CAD) in Japanese patients, we conducted a case-control study with 158 Japanese patients and 169 control subjects. The frequencies of HPA-2 polymorphism and the variable number of tandem repeat (VNTR) polymorphisms in the macroglycopeptide region did not significantly differ between CAD patients and control subjects. The polymorphisms of GPIb alpha were not associated with the number of affected vessels in CAD patients. When patients with acute coronary syndrome only were analyzed, the frequencies of the two polymorphisms of GPIb alpha showed no significant difference. Although plasma von Willebrand antigen (vWF:Ag) levels in patients were significantly higher than in controls, no association between vWF concentration and GPIb genotypes was observed. In patient groups with higher or lower vWF:Ag concentrations, no increase in the frequencies of Met145 or larger VNTR polymorphisms was seen in either group. Our findings indicate that no association exists between the frequencies of the two polymorphisms of GPIb alpha and CAD.

Aged↗

PubMed1999

Variability in phenylephrine response and essential hypertension: a search for human alpha(1B)-adrenergic receptor polymorphisms.

Genetic polymorphisms in drug receptors, in particular adrenergic receptors, may contribute to intersubject differences in pharmacologic response. We tested patients and first-degree normotensive and hypertensive relatives of patients with essential hypertension and found substantial intersubject variability in blood pressure response to infusion of the alpha(1)-adrenergic agonist phenylephrine. Because response to phenylephrine depends upon interaction with alpha(1B)-adrenergic receptors, we tested whether polymorphisms in this receptor contribute to the variable responses. Accordingly, we developed a polymerase chain reaction-based method, generating four exon-spanning fragments, to identify polymorphisms in the coding sequence of the two exons of the human alpha(1B)-adrenergic receptor. We sequenced the entire coding sequence of exon 1 from 51 subjects and exon 2 from 16 of these 51 subjects. Compared with the published sequence for the alpha(1B)-adrenergic receptor, we found one amino acid addition in exon 2 at position 368 (Arg) and one substitution (Arg371Gly) in all subjects. We thus suggest we have defined the correct coding sequence of the human alpha(1B) receptor. We found two "silent" polymorphisms in exon 1, one of which occurred in 3 of 51 subjects. These polymorphisms were unrelated to blood pressure status or response to phenylephrine. The 95% confidence intervals for expression of polymorphisms in exons 1 and 2 were 0 to 11%. Our data reveal that although phenylephrine response varies in humans, frequent polymorphisms in the coding sequence of the human alpha(1B)-adrenergic receptor appear not to account for this variation or for the increased blood pressure in patients with essential hypertension.

Adult↗

PubMed1999

Coding block and 5 leader cistron polymorphisms of the beta2-adrenergic receptor.

The gene encoding the beta2-adrenergic receptor (beta2AR) is highly polymorphic in the human population. Common polymorphisms in the receptor coding block (amino acids 16 and 27) affect agonist-promoted downregulation. Another common polymorphism in the 5' leader cistron of the beta2AR gene also regulates receptor expression, but does so through a mechanism that is independent of agonist exposure. None of these polymorphisms appears to be causative factor for asthma. However, data from several studies now indicate that the asthmatic phenotype and therapeutic response may be modified by the different polymorphic variants. This modifying effect is not likely due to a single dominant polymorphic locus, but rather the result of interaction among multiple polymorphic loci that regulate receptor expression through different mechanisms.

Animals↗

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↗

PubMed1999

Frequency of functionally important beta-2 adrenoceptor polymorphisms varies markedly among African-American, Caucasian and Chinese individuals.

There are ethnic differences in the prevalence and severity of hypertension and asthma and in beta-2 adrenergic receptor (BAR2)-mediated vascular responses. Two common polymorphisms of the human BAR2, Arg16 to Gly and Gln27 to Glu, are associated with alterations in BAR2 response, both in vitro and in vivo. Ethnic differences in disease manifestations and responses to treatment may be explained by the altered frequency of BAR2 polymorphisms. To determine the relative frequencies of the Arg16 to Gly and Gln27 to Glu BAR2 polymorphisms in different ethnic groups we studied 415 (123 African-American, 188 Caucasian-American and 104 Chinese) healthy individuals. There was a marked interethnic difference in the frequency of the BAR2 polymorphisms among the ethnic groups. The Glu27 allele was more frequent in Caucasian-American (34.8%) than in African-American individuals (20.7%) (P = 0.0001) and much less frequent in Chinese individuals (7.2%) (P = 0.0001 versus African-American or Caucasian-American). The homozygous Glu27 genotype was more frequent in Caucasian-American (15.4%) than African-American individuals (4.9%) (P = 0.003) and was not observed in Chinese. The Gly16 allele (54.3% versus 41.3%) and homozygous genotype (35.1% versus 18.3%) were more common in Caucasian-American than Chinese individuals (P = 0.003 for both). There is a marked ethnic difference in the frequency of these two common BAR2 polymorphisms among African-American, Caucasian-American and Chinese individuals, with a markedly reduced frequency of the Glu27 polymorphism, the polymorphism associated with resistance to desensitization and increased BAR2 responses, in African-American and Chinese individuals. Such ethnic genotypic differences may explain previously observed alterations in the response to the BAR agonists in different ethnic groups.

Black or African American↗

PubMed2000

Lack of association of angiotensin-converting enzyme and angiotensinogen genes polymorphisms with left ventricular structure in young normotensive men.

Left ventricular (LV) hypertrophy is a strong predictive factor for cardiovascular morbidity and mortality. LV structure and function are influenced by many variables, including genetic background. The potential role of gene polymorphisms of different components of the renin angiotensin system remains controversial. The aim of this study was to determine the influence of deletion/insertion (D/I) polymorphism of the angiotensin-converting enzyme (ACE) gene and M235-->T polymorphism of the angiotensinogen (AG) gene on left ventricular morphology and function in young normotensive men. The study included 110 normotensive healthy males (mean age 24 +/- 4 years, age range 18 to 34 years) who were assessed by echocardiography for LV structure and function. In all subjects ACE D/I polymorphism was evaluated using a polymerase chain reaction (PCR) method. M235-->T polymorphism assessment was available in 98 individuals. Significant differences between groups according to ACE I/D or AG M235-->T polymorphisms were not found for parameters of LV morphology or for parameters of systolic and diastolic function. When subjects with DD or ID genotypes were grouped, their LV mass index was higher than that in subjects with II genotypes (86 +/- 14 vs 79 +/- 15, r = 0.033, p = 0.05). There were no significant differences among other variables. In a population of young normotensive men where the influence of confounding variables such as age, gender and associated pathological conditions is minimized, the gene polymorphisms of ACE I/D and AG M235-->T are not important determinants of LV structure and function.

Adult↗

PubMedDate not supplied

Apolipoprotein(a) polymorphism and its association with plasma lipoprotein(a) levels: a north Indian study.

Elevated levels of lipoprotein(a) has been regarded as an independent risk factor for coronary, peripheral and cerebral atherosclerosis. The enormous intra-personal variation in the plasma concentration of lipoprotein(a) is almost entirely controlled by the apolipoprotein(a) i.e. gene locus on the chromosome 6q 26-27. The apolipoprotein(a) molecule is highly polymorphic and is known to exist in multiple, genetically determined isoforms. These polymorphisms may be responsible for difference in promoter activity, variable size of apolipoprotein(a) and thereby variation in plasma lipoprotein(a) concentration. We studied the effect of two types of polymorphisms, (i) variation in length of the pentanucleotide repeat in the 5' flanking region starting -1373 bp upstream of AUG codon, and (ii) the Kringle-4 type 2 size polymorphism, on plasma lipoprotein(a) levels in North Indian population. The study group consisted of 88 angiographically assessed male coronary artery disease patients (age range 30-70 years) and 83 age- and sex-matched healthy controls. The pentanucleotide repeat polymorphism was analysed using polymerase chain reaction. In all, 8/11 pentanucleotide repeat isoforms were observed. Using SDS-agarose gel electrophoresis and immunoblotting isoforms having 12-50 Kringle-4 type 2 repeats were detected. Our study indicates a strong association of elevated plasma lipoprotein(a) concentration with coronary artery disease. An inverse correlation was seen between lipoprotein concentration and isoform size for both the pentanucleotide repeat polymorphism and the Kringle-4 type 2 polymorphisms; statistically significant difference (p = 0.001) was, however, observed only for the later.

Adult↗

PubMed2000

[Cytochrome P450 1A1 and cytochrome P450 2E1 gene polymorphisms in Guangzhou Hans].

OBJECTIVE: To determine the distribution of cytochrome P450 1A1(CYP1A1) and cytochrome P450 2E1(CYP2E1) gene polymorphisms in Guangzhou Hans. METHODS: A total of 150 healthy Guangzhou Hans were studied with PCR-RFLP and ASA techniques. Current results were compared with the data on other ethnic groups. RESULTS: In the 150 individuals tested, the frequencies of the m1(Msp I-) and m2(Msp I+) alleles of the Msp I polymorphic site in the 3' non-coding region of the CYP1A1 gene were found to be 62.33% and 37.67%, respectively. The observed frequencies of the m1m1, m1m2 and m2m2 genotypes were found to be 40%, 44.67% and 15.33%, respectively, which met Hardy-Weinberg equilibrium. The frequencies of the A and G alleles of the exon 7 A4889G polymorphic site in the CYP1A1 gene were found to be 79% and 21%, respectively. The observed frequencies of the AA, AG and GG genotypes were found to be 62.67%, 32.67% and 4.66%, respectively, which met Hardy-Weinberg equilibrium. A close linkage between the Msp I polymorphism and exon 7 A4889G polymorphism was observed in Guangzhou Hans(chi(2)=62.2358, P<0.005). The frequencies of the C1(Rsa I+, Pst I-) and C2(Rsa I-, Pst I+) alleles of the Rsa I polymorphic site in the 5' flanking region of the CYP2E1 gene were found to be 85.3% and 14.7%, respectively. The observed frequencies of the C1C1, C1C2 and C2C2 genotypes were found to be 67.3%, 29.3%, and 3.4%, respectively, which met Hardy-Weinberg equilibrium. CONCLUSION: The frequencies of the CYP1A1 and CYP2E1 gene polymorphisms in Guangzhou Hans were similar to those in Japanese population, but were significantly different from those in European populations.

China↗

PubMed2000

Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism is not associated with breast cancer.

The antigen content of plasminogen activator inhibitor-1 (PAI-1) in primary breast cancer tissue extracts may be of strong prognostic value: high levels of PAI-1 in tumors predict poor prognosis for patients. The gene encoding PAI-1 is highly polymorphic and an insertion (5G)/deletion (4G) polymorphism in the PAI-1 gene promoter (the 4G/5G polymorphism), may have functional significance in PAI-1 expression. In the present work the distribution of genotypes and frequency of alleles of the 4G/5G polymorphism in subjects with breast cancer were investigated. Tumor tissues were obtained from 100 postmenopausal women with node-negative and node-positive ductal breast carcinoma with uniform tumor size. Blood samples from age matched healthy women served as control. The 4G/5G polymorphism was determined by PCR amplification using the allele specific primers. The distribution of the genotypes of the 4G/5G polymorphism in both control and patients did not differ significantly (P > 0.05) from those predicted by the Hardy-Weinberg distribution. There were no differences in the genotype distributions and allele frequencies between node-positive and node-negative patients. The 4G/5G polymorphism may not be linked with elevated level of PAI-1 observed in breast cancer and therefore may not be associated with appearance and/or progression of breast cancer.

Adult↗

PubMed1998

[Insulin receptor substrate-1 and glucose transporter gene polymorphisms in noninsulin-dependent diabetes mellitus].

OBJECTIVE: To evaluate the role of insulin receptor substrate-1 (IRS-1) and glucose transporter-1 (GLUT1) gene polymorphisms in Chinese patients with noninsulin-dependent diabetes mellitus (NIDDM) and diabetic neophropathy (DN). METHODS: Aminoacid polymorphism in codon 972 of IRS-1 gene and the polymorphic Xba I site of GLUT1 gene were analyzed by PCR-RFLP in 131 patients with NIDDM and 124 normal subjects. DN was defined as persistent albuminuria and/or impaired renal function, without known cause of renal diseases other than diabetes. Insulin sensitivity index (ISI) and body mass index (BMI) were also calculated. RESULTS: The distribution of IRS-1 gene polymorphism showed no difference between patients with NIDDM and normal controls. The frequencies of Xba I (+/-) genotype (59% vs. 33%, P < 0.01) and Xba I (-) allele (37% vs. 21%, P < 0.01) were significantly higher in NIDDM patients than in normal subjects. To further explore the linkage of GLUT1 gene polymorphism with DN, we examined the GLUT1 genotype of NIDDM patients with or without renal damage. The frequency of Xba I (+/-) genotype (75% vs. 44%, P < 0.01) and Xba I (-) allele (44% vs. 29%, P < 0.05) was significantly higher in NIDDM patients with diabetic nephropathy than either those without nephropathy or normal subjects. However, there were no significant differences of GLUT1 genotype and allele frequency in NIDDM patients without nephropathy and normal controls. The presence of Xba I (-) allele appeared to have a strong association with the development of diabetic nephropathy. The odds ratio was 1.915, and the 95% confidence interval was 1.044-3.514. The association of Xba I (-) allele of GLUT1 gene with NIDDM partly reflected their close association with DN. Although there was no correlation between the gene polymorphism of GLUT1 and BMI, patients carrying the Xba I (-) allele showed a lower ISI. CONCLUSION: No association was found between the gene polymorphism of IRS-1 and NIDDM. THe Xba I (-) allele of GLUT1 gene might be taken as a genetic marker of NIDDM with diabetic nephropathy and this genetic susceptibility appears to be associated with the insulin resistance in patients with NIDDM.

Adult↗

PubMed2001

The promoter polymorphism of the interleukin-6 gene regulates interleukin-6 production in neonates but not in adults.

In the promoter region of the IL-6 gene there is a single base exchange (G --> C) polymorphism at position -174. Recent findings suggest that this polymorphism may affect the transcription rate of the IL-6 gene and IL-6 plasma levels. To analyse its biological significance, we examined IL-6 plasma levels in cord blood and IL-6 production by neonatal cells after LPS-stimulation in relation to the presence of the IL-6G and IL-6C alleles. We hypothesized that since healthy neonates lack a previous exposure to exogenous antigens, their cytokine production could be genetically regulated. We also assumed that the normal labour-related stress could provide a physiological stimulus for IL-6 production. Cord blood was collected from 50 healthy, full-term neonates after normal vaginal delivery (VD) and from 42 healthy, full-term neonates after elective caesarean section (ECS). Adult samples were obtained from 450 healthy adult controls. The -174 polymorphism was analysed using PCR. IL-6 plasma levels and in vitro IL-6 production were measured using an ELISA method. Generally, IL-6 plasma levels in neonates were significantly higher than those in adults (neonates born by VD versus adults p < 0.001 and neonates born by ECS versus adults p < 0.001); the median value for neonates born by VD was 11.4 pg/ml (4.5-45.9), for neonates born by ECS 2.9 pg/ml (1.9-6.4) and for adults, 1.2 pg/ml (0.7-2.0). Surprisingly, cord blood IL-6 levels after VD differed significantly from those after ECS (p < 0.001). An analysis was carried out to ascertain if there was a genetic association between different IL-6 genotypes and IL-6 plasma levels in neonates. In the group of VD neonates with the CC genotype, non-carriers of the G allele, secreted significantly more IL-6 than carriers of the G allele (p < 0.03); 21.4 pg/ml (9.5-81.3) and 9.6 pg/ml (3.5-36.2) respectively. In line with this, ECS newborns with the CC genotype had higher IL-6 plasma levels than carriers of the G allele (p < 0.02); respective median values were 6.3 pg/ml (2.2-12.9) and 2.7 pg/ml (1.7-4.1). These findings were also supported when in vitro IL-6 production by neonatal mononuclear cells was compared carriers of the G allele and non-carriers of the G allele. IL-6 levels were significantly lower in carriers of the G allele than in non-carriers (p < 0.04); respective median values were 6,980 pg/ml (4,175-16,800) and 17,425 pg/ml (11,400-33,900). In vivo or in vitro production of IL-6 of adult controls was not associated with the IL-6 -174 polymorphism. The difference between cord blood IL-6 levels after VD and after ECS suggests that normal labour-related stress induces IL-6 production. Our data also suggest that the -174 polymorphism of the IL-6 gene participates in the regulation of IL-6 responses in both groups of neonates. Furthermore, the naive IL-6 response of stimulated neonatal cells is associated with the -174 polymorphism of the IL-6 gene. In healthy adults, the regulation of IL-6 responses differs from that of healthy neonates, since baseline and inducible IL-6 levels in adults were not associated with this polymorphism. This indicates that the genetic regulation of IL-6 production can be observed in naive cells, while in adult cells previous contact with exogenous antigens probably modifies their responses.

Adult↗

PubMed2001

The association study of DRD2, ACE and AGT gene polymorphisms and metamphetamine dependence.

We investigated the association between metamphetamine dependence and TaqI A polymorphism of the dopamine receptor D2 gene (DRD2), I/D polymorphism in angiotensin-converting enzyme (ACE) and M235T polymorphism of the angiotensinogen gene (AGT) in 93 unrelated metamphetamine-dependent subjects and 131 controls. Our results did not prove any association of TaqI A polymorphism of the DRD2 gene, I/D polymorphism of ACE gene, and M235T polymorphism of AGT gene with the metamphetamine dependence in Caucasians of Czech origin. However, a significant difference in allele I frequency between male and female control groups for the I/D ACE polymorphism (p<0.03) was found.

Adult↗

PubMed2001

[Platelet glycoprotein IIb/IIIa (LeuPro 33) polymorphism in stroke patients].

This is the first Hungarian paper on the platelet glycoprotein IIb/IIIa (LeuPro 33) polymorphism in stroke patients. There are conflicting data about the role of this polymorphism in the pathogenesis of arterial thrombosis. The aim of our study was to describe the prevalence of PLA1/PLA2 in healthy persons and in stroke patients. From the same study population other polymorphism (prothrombin gene 20210 G/A) also has been determined. Blood sample was investigated by polymerase chain reaction in 173 unrelated healthy donors and 234 stroke patients. Stroke was documented by CT and MRI. We used a rutin questionnaire to study previous vascular events and conventional risk factors of patients. Prevalence of PLA1/PLA2 was 23.5% among healthy persons. That is higher than in other European countries (15%). It was 30.4% in stroke patients (OR: 1.42, 95%; CI: 0.87-2.31; p = 0.15). Heterozigous PLA was found in patients older than 50 by 33.6% (OR: 1.65, 95%; CI: 0.94-2.87; p = 0.09). Previous vascular events and conventional risk profil were not significantly different between PLA1/PLA1 and PLA1/PLA2 groups of patients. In patients under 50 having 20-85% stenosis of internal carotid artery there was a higher prevalence (p = 0.09). Comparing stroke patients to control population there was a slight increase (OR: 7.0; p = 0.06) in the frequency of two polymorphisms (PLA and factor II) together in the stroke cases. Polymorphism of GP IIb/IIIa LeuPro 33 seemed to be increased in stroke patients above 50 years. Carotid stenosis with polymorphism is a risk factor for young patients. PLA variant together with prothrombin gene polymorphism results very high risk for stroke.

Adult↗