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PubMed2005

Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in Xinjiang, China.

AIM: To analyze the relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh's esophageal squamous cell cancer in China. METHODS: The genotypes of cytochromes P450 (CYP) 2E1 and glutathione S-transferase (GST) M1 were investigated by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) following PCR in 104 Kazakh's patients with esophageal cancer (EC) and 104 non-cancer controls. RESULTS: The frequency of CYP2E1 c1/c1 genotype was significantly higher in patients with cancer (77.9%) than in control subjects (24.0%) (P<0.05; OR, 11.13; 95%CI, 5.84-21.22). The difference of GSTM1 null was significantly more frequent in the cancer (34.6%) vs the control group (3.8%) (P<0.05; OR, 13.24; 95%CI, 4.50-38.89). On the other hand, the combination of GSTM1 presence and CYP2E1 c1/c1 genotypes increased the risk for cancer (P<0.05; OR, 13.42; 95%CI, 6.29-28.3). CONCLUSION: The CYP2E1 c1/c1, GSTM1 deletion genotypes are genetically susceptible biomarkers for ESCC in Kazakh population. Individuals with allele c1 of RsaI polymorphic locus for CYP2E1 may increase the risk of ESCC. Moreover, CYP2E1 wild type (c1/c1) increased the susceptibility to ESCC risk in Kazakh individuals with GSTM1 presence genotype.

Aged↗
PubMed1999

Plasma carotenoids, glutathione S-transferase M1 and T1 genetic polymorphisms, and risk of hepatocellular carcinoma: independent and interactive effects.

This study was conducted to assess the role of carotenoid and glutathione S-transferase (GST) M1 and T1 genetic polymorphisms in the development of hepatocellular carcinoma (HCC). A total of 84 incident cases of HCC and 375 matched controls selected from a cohort of 7,342 men (4,841 chronic hepatitis B carriers and 2,501 noncarriers) who were recruited between 1988 and 1992 in Taiwan were studied. Neither GST M1/T1 polymorphisms nor plasma levels of various carotenoids were independently associated with HCC, but they modulated smoking- and/or drinking-related HCC risk. Cumulative exposure to tobacco smoke significantly increased HCC risk in a dose-dependent manner among subjects with low plasma beta-carotene levels (p for trend = 0.047) but not among those with high levels. A statistically significant effect of habitual alcohol drinking on HCC risk was observed only for those with low plasma levels of beta-carotene, alpha-carotene, or lycopene and for GST M1 null subjects. There was evidence suggesting an interaction between the GST M1/T1 genotype and certain carotenoids in HCC associated with smoking and drinking. The strongest effect of smoking and drinking was noted among GST M1 null subjects with low plasma levels of beta-carotene (smoking: adjusted odds ratio (OR) = 3.54, 95% confidence interval (CI) 1.06-11.83; drinking: OR = 8.28, 95% CI 2.40-28.61).

Adult↗
PubMed1997

Analysis of the genetic polymorphism between three Streptococcus thermophilus strains by comparing their physical and genetic organization.

The physical maps of Streptococcus thermophilus CNRZ368 and NST2280 strains were constructed by analysing PFGE patterns obtained with the low-frequency-cutting enzymes SmaI, BssHII and SfiI. Their chromosomes are 1864 and 1840 kb circular molecules, respectively. Comparison of their physical maps with that of the reference A054 strain revealed a relatively conserved organization of the restriction sites. Three variable regions were detected with the map of CNRZ368 whereas 15 were found with the map of NST2280. To construct the genetic maps, probes corresponding to 10 single-copy genes, the rrn genes and the insertion sequences IS1191, IS981 and ISS1 were hybridized to Southern blots of chromosomal DNA digested with the different mapping enzymes. Comparison of the genetic maps of the three strains showed a conserved location of the mapped single-copy genes. However, six rrn loci were present in the chromosome of A054 and CNRZ368 whereas five were present in the NST2280 chromosome. A polymorphism was also found in the copy number of the insertion sequences between the three strains.

Chromosome Mapping↗
PubMed2006

Genetic polymorphisms of human ABC transporter ABCG2: development of the standard method for functional validation of SNPs by using the Flp recombinase system.

The vector-mediated introduction of cDNA into mammalian cells by calcium phosphate co-precipitation or permeation with lipofectamine is widely used for the integration of cDNA into genomic DNA. However, integration of cDNA into the host's chromosomal DNA occurs randomly at unpredictable sites, and the number of integrated recombinant DNAs is not controllable. To investigate the effect of genetic polymorphisms of ABCG2 on the protein expression and the drug resistance profile, we developed the Flp-In method to integrate one single copy of ABCG2 variant-cDNA into FRT-tagged genomic DNA. More than 20 metaphase spreads were examined for both fluorescence in situ hybridization (FISH) mapping and multicolor-FISH analysis, and it has been revealed that ABCG2 cDNA was incorporated into the telomeric region of the short arm on one of chromosomes 12 in Flp-In-293 cells. Based on the currently available SNP data for human ABCG2, we have created a total of seven variants by site-directed mutagenesis and stably expressed them in Flp-In-293 cells. While mRNAs of those integrated ABCG2 variants and wild type were evenly expressed in Flp-In-293 cells, the protein expression levels of F208S and S441N variants were found to be markedly low. It is suggested that the protein instability due to enhanced degradation resulted in the low levels of their protein expression. Thus, the Flp recombinase system would provide a useful tool to validate the effect of nonsynonymous SNPs on the protein stability and post-translational modification of ABCG2.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed1988

Genetic polymorphism of a lymphocyte protein (p75) with six different alleles studied by two-dimensional electrophoresis: qualitative and quantitative data.

The genetic polymorphism of a human lymphocyte protein (p75) was studied by two-dimensional electrophoresis within 17 families and, in addition, 22 unrelated individuals from Southern Germany, resulting in a total of approximately 100 individuals. The cytosolic and membrane proteins from cell lysates of phytohemagglutinin stimulated and [3H]leucine labeled lymphocytes were separated by two-dimensional electrophoresis. The p75 protein with an approximate molecular weight of 75,000 occurred in six variants with slightly different isoelectric points and/or apparent molecular weights. Three common variants (a, b, and c) and three rare variants (d, e and f) could be distinguished. Among the approximately 100 individuals studied we observed 15 different phenotypes, three homozygous (p75-a, -b, -c) and 12 heterozygous (p75-ab, -ac, -bc, -ad, -ae, -be, -bf, -cd, -ce, -cf, -de, -df) phenotypes. The genetics of the p75 protein variations was ascertained by family studies and quantitative computer analysis. We were able to show a Mendelian mode of inheritance of the variants within the families and a gene-dosage dependence of the protein spots in homozygous and heterozygous phenotypes. The data allowed us to assume a polymorphic protein p75 determined by six alleles on a autosomal gene locus. The allele frequencies were calculated from the phenotype distribution within 56 unrelated individuals. The gene frequencies of the three common alleles ranged between 0.38 and 0.22 and the gene frequencies of the three rare alleles ranged between 0.01 and 0.07.

Alleles↗
PubMed2005

[Innate immunity, receptors for exogenous and endogenous danger patterns in immunopathogenesis of atherosclerosis--part II: TLR receptors, significance of genetic polymorphism of danger signals receptors].

The most important set of receptors for danger patterns are TLR receptors. Together ten different TLR receptors were identified so far. Majority of TLR receptors is expressed on the cell surface to identify extracellulary localized danger signals. Some TLR receptors are also expressed in the intracellular compartment to identify intracellular danger signals. Receptors for danger signals display individual differences delineated by genetic polymorphism. The individual immune reactivity is developed in the context of genetic predisposition and the exposition to variable environmental factors. The differences in an individual immune reactivity are probably responsible for individual susceptibility or resistance to the development of immunopathological reactivity, which is involved in the immunopathogenesis of atherosclerosis.

Animals↗
PubMedDate not supplied

Genetic polymorphisms and clinical practice: the example of osteoporosis.

Over the past decades epidemiological research of so-called "complex" diseases, such as diabetes, osteoporosis, cancer, and cardiovascular disease, has identified a number of risk-factors for these common age-related disorders. Examples include obesity for diabetes, low bone mineral density for osteoporosis, and smoking for cancer and cardiovascular disease. Some of these risk factors are used in clinical practice, for example to identify subjects-at-risk and for monitoring treatment of patients with these diseases. More recently, a novel class of risk factors, genetic polymorphisms, has gained considerable interest in this respect. This is mostly due to the Human Genome Project which has identified every human gene and also uncovered a plethora of polymorphic variants of these genes which embody the genetic risk factors. Genetic risk factors are expected to find applications in early identification of subjects-at-risk, prediction of response-to-treatment, and development of novel therapeutic options. We will here discuss some developments in the field of the genetics of osteoporosis.

Humans↗
PubMed1997

Association of prostate cancer risk with genetic polymorphisms in vitamin D receptor and androgen receptor.

BACKGROUND: Prostate cancer is an increasingly common disease for which there are few well-established risk factors. Family history data suggest a genetic component; however, the majority of prostate cancer cases cannot be explained by a single-gene model. Prostate cell division is influenced by two steroid hormones, testosterone and vitamin D, the action of each being mediated by its respective receptor. The genes for the two receptors are candidates in a multigenic model for prostate cancer susceptibility. PURPOSE: We examined genetic polymorphisms in two steroid receptors, the androgen receptor (AR) and the vitamin D receptor (VDR), in a case-control pilot study of prostate cancer. METHODS: Fifty-seven non-Hispanic white case patients with prostate cancer and 169 non-Hispanic white control subjects were genotyped for a previously described microsatellite (CAG repeats) in the AR gene and for a newly discovered poly-A microsatellite in the 3'-untranslated region (3'UTR) of the VDR gene. To compare genotypes with respect to prostate cancer risk, we estimated odds ratios (ORs) by using logistic regression. ORs were also estimated separately for advanced and localized cases of disease. All P values resulted from two-sided tests. RESULTS: Both the AR and the VDR polymorphisms were associated, individually and after mutual adjustment, with prostate cancer. Adjusted ORs (95% confidence intervals [CIs]) for prostate cancer were 2.10 (95% CI = 1.11-3.99) for individuals carrying an AR CAG allele with fewer than 20 repeats versus an allele with 20 or more repeats and 4.61 (95% CI = 1.34-15.82) for individuals carrying at least one long (A18 to A22) VDR poly-A allele versus two short (A14 to A17) poly-A alleles. For both the AR and VDR genes, the at-risk genotypes were more strongly associated with advanced disease than with localized disease. CONCLUSIONS: In this pilot study, genetic variation in both the VDR and the AR genes was associated with prostate cancer, and both genes appear to preferentially confer risk for advanced disease. These two genetic risk factors, if confirmed, are among the strongest risk factors yet identified for prostate cancer. IMPLICATIONS: These results are consistent with a multigenic model of prostate cancer susceptibility. On the basis of the joint effect of several genetic loci, one might ultimately be able to construct a risk profile to predict advanced disease, so that men whose disease is unlikely to progress to an advanced stage can possibly be spared aggressive treatment.

Alleles↗
PubMed2004

CYP1A1, GSTM1 and GSTT1 genetic polymorphism is associated with susceptibility to polycystic ovaries in South Indian women.

Polymorphic variants in the phase I enzyme, cytochrome P450 gene, may lead to increased toxification, whereas polymorphisms in the phase II enzyme, glutathione S-transferase genes, may result in impaired detoxification. Alterations in the activities of phase I drug metabolizing enzymes and phase II detoxification enzymes may cause abnormal functioning and formation of follicular cysts in the ovaries and thus causing an imbalance in the hormone profiles. This study aimed to investigate the relationship between genetic polymorphisms of CYP1A1 (T6235C), GSTM1 and GSTT1 in South Indian women with polycystic ovaries (PCO) using polymerase chain reaction-restriction fragment length polymorphism. The frequencies of variants of these genes were studied in 180 women with confirmed PCO and in 72 healthy fertile women with successful pregnancy record. No significant difference was found between the frequencies of GSTM1 and GSTT1 null genotypes in PCO cases and healthy controls. However, CYP1A1 Msp I homozygous mutants were strongly associated (P = 0.0139) with increased susceptibility to PCO. Three genotype combinations, CYP1A1 (mt/mt) with GSTM1 [-] and GSTT1 [-], CYP1A1 (wt/mt) with GSTM1 [-] and GSTT1 [-] and CYP1A1 (mt/mt) with GSTM1 [-], GSTT1 [+], were also observed in women with PCO. In conclusion, the presence of hyperinducible CYP1A1 (T6235C) mutant genotype and its mutants in combination with GSTM1 and GSTT1 null genotypes might cause an imbalance between phase I and phase II enzymes, and therefore may represent a risk factor for PCO.

Adolescent↗
PubMed2005

[Genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population].

In order to study the genetic polymorphisms of nucleotide repair gene hMTH1 in southern Chinese Han population, the polymorphisms of the gene's promoter and its five exons among peripheral blood lymphocytes of 172 Chinese Han people were analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and DNA sequencing. The sequences of the promoter and exon 1 of hMTH1 gene were conserved. A T to C polymorphism was detected at the 73th base in exon 2. The genotype frequencies of TT and TC were 93.02% and 6.98%, respectively. The allelic frequencies of T and C were 96.51% and 3.49%, respectively. A T to C polymorphism was detected at codon 45 in exon 3, which was first reported. The genotype frequencies of TT and TC were 95.35% and 4.65%, respectively. The allelic frequencies of T and C were 97.67% and 2.33%, respectively. A G to A polymorphism was detected at codon 83 in exon 4. The genotype frequencies of GG and GA were 89.53% and 10.47%, respectively. The allelic frequencies of G and A were 94.77% and 5.23%, respectively. A C to T polymorphism was detected at codon 119 in exon 5. The genotype frequencies of CC and CT were 95.93% and 4.07%, respectively. The allelic frequencies of C and T were 97.97% and 2.03%, respectively.

Asian People↗
PubMed1980

Genetic polymorphism of human plasminogen.

Using isoelectric focusing (IEF) in polyacrylamide gel of neuraminidase-treated serum or plasma samples and immunofixation or caseinolytic overlay after urokinase activation of gels, a common genetic polymorphism in human plasminogen has been delineated. Two alleles PLGN*A and PLGN*B, were observed with gene frequencies in whites of .69 and .30; in Orientals of .96 and .03; and in blacks of .80 and .18. Several rare alleles were also found. The distribution of phenotypes fits the Hardy-Weinberg equilibrium. Inheritance is autosomal codominant and fits the expectations of Mendelian inheritance. There is fetal synthesis, but no transplacental passage of plasminogen in either direction.

Adult↗
PubMed1991

N-acetylation of aromatic amines: genetic polymorphism in inbred rat strains.

The inheritance of rat liver N-acetyltransferase polymorphism was investigated with reciprocal genetic crosses between slow (NSD/N) and rapid (Peth/N) acetylator strains. Rat liver N-acetyltransferase activity was determined using a spectrophotometric assay which measured the amount of arylamine substrate present after incubation with N-acetyltransferase in vitro. Male N-acetyltransferase activities assayed in liver preparations using p-aminobenzoic acid and p-toluidine as substrates indicate bimodality of the parental strains and unimodality of the F-1 generation; limited data suggest trimodality (not significantly different from a 1:2:1 ratio) of the F-2 generation. Reciprocal crosses of WKY/N, another slow acetylator strain, and the Peth/N strain gave results similar to those of the NSD/N x Peth/N cross. Female N-acetyltransferase activities in all strains studied were lower than male N-acetyltransferase activities, but were similarly distributed in the parental and F-1 generations. The male/female N-acetyltransferase activity ratio was substrate- and genotype-dependent. Results show that regulation of the variation of rat liver N-acetyltransferase activity is consistent with autosomal Mendelian inheritance of two major alleles at a single gene locus.

4-Aminobenzoic Acid↗
PubMed2000

Interindividual variation in CYP1A1 expression in breast tissue and the role of genetic polymorphism.

The cytochrome P4501A1 (CYP1A1) enzyme is regulated at the transcriptional level and its expression is influenced by genetic factors, polymorphisms in the structural and regulatory genes, and by environmental factors such as exposure to polycyclic aromatic hydrocarbons (PAHs). To investigate the role of CYP1A1 in breast cancer, we studied CYP1A1 expression in breast tissue, thereby taking all possible modifying factors into account. We measured CYP1A1 expression in 58 non-tumor breast tissue specimens from both breast cancer patients (n = 26) and cancer-free individuals (n = 32) using a newly developed reverse transcription-polymerase chain reaction assay. CYP1A1 expression varied between specimens approximately 400-fold and was independent of age. CYP1A1 expression was somewhat higher in tissue from breast cancer patients than in that from cancer-free individuals, but this difference was not statistically significant. Analysis for CYP1A1 genetic polymorphisms revealed eight variants, seven in the cancer-free group and one in the patient group. The variant genotype was not a good predictor of expression level. We conclude that high CYP1A1 expression could be a risk factor for breast cancer and that the known CYP1A1 polymorphisms are not good predictors of CYP1A1 expression.

Adolescent↗
PubMed2002

[Genetic polymorphism of UDP-glucuronosyltransferase 1F and susceptibility to hepatocellular carcinoma].

OBJECTIVE: To study the genetic polymorphisms of UDP-glucuronosyltransferase 1F(UGT1F) and the relationship between polymorphisms and susceptibility to hepatocellular carcinoma (HCC). METHODS: The polymorphisms of UGT1F of 84 patients with HCC and 144 healthy controls were detected by PCR-denaturation gradient gel electrophoresis-sequencing or PCR-single strain conformation polymorphsim-sequencing. RESULTS: Three new single nucleotide polymorphisms(SNP) were found: the first one was a transversion of TrarrG at nucleotide 232; the second one was the transition of ArarrG at nucleotide 528 in exon 1; the last one was the transition of ArarrG at nucleotide 376 in intron 2. Additionally, the polymorphism at nucleotide 754 was proved in this study. The frequencies of genotype and allele of 4 loci in cases and controls were analyzed. Both frequencies of genotype G/G(13.10%) and allele G (29.17%) of position 754 of UGT1F in cases were sig nificantly greater than those in controls (2.78% and 19.44% ) respectively. For other loci, the difference between the two groups were not significant. CONCLUSION: Exons 2-5 of UGT1F are highly conservative, but exon 1 emerges highly polymorphic. And the polymorphism at locus 754 may be related with HCC.

Alleles↗
PubMed1997

Contribution of genetic polymorphism in the renin-angiotensin system to the development of renal complications in insulin-dependent diabetes: Genetique de la Nephropathie Diabetique (GENEDIAB) study group.

Diabetic nephropathy is a glomerular disease due to uncontrolled diabetes and genetic factors. It can be caused by glomerular hypertension produced by capillary vasodilation, due to diabetes, against constitutional glomerular resistance. As angiotensin II increases glomerular pressure, we studied the relationship between genetic polymorphisms in the renin-angiotensin system-angiotensin I converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II, subtype 1, receptor-and the renal involvement of insulin-dependent diabetic subjects with proliferative retinopathy: those exposed to the risk of nephropathy due to diabetes. Of 494 subjects recruited in 17 centers in France and Belgium (GENEDIAB Study), 157 (32%) had no nephropathy, 104 (21%) incipient (microalbuminuria), 126 (25 %) established (proteinuria), and 107 (22%) advanced (plasma creatinine > or = 150 micromol/liter or renal replacement therapy) nephropathy. The severity of renal involvement was associated with ACE insertion/deletion (I/D) polymorphism: chi2 for trend 5.135, P = 0.023; adjusted odds ratio attributable to the D allele 1.889 (95% CI 1.209-2.952, P = 0.0052). Renal involvement was not directly linked to other polymorphisms. However, ACE I-D and AGT M235T polymorphisms interacted significantly (P = 0.0166): in subjects with ACE ID and DD genotypes, renal involvement increased from the AGT MM to TT genotypes. Thus, genetic determinants that affect renal angiotensin II and kinin productions are risk factors for the progression of glomerular disease in uncontrolled insulin-dependent diabetic patients.

Adult↗
PubMed1999

Association between N-acetyltransferase 2 (NAT2) genetic polymorphism and development of breast cancer in post-menopausal Chinese women in Taiwan, an area of great increase in breast cancer incidence.

The incidence of breast cancer has increased greatly in Taiwan over the past 2 decades. Increased exposure to environmental carcinogens, including aryl aromatic amines, as a result of the economic boom, is suspected to be one factor contributing to this increase. The enzyme N-acetyltransferase 2 (NAT2) determines the rate of metabolism of aryl aromatic amines, and therefore the NAT2 slow acetylator genotype is associated with an increased risk of cancer. Our present case-control study of 150 breast cancer patients and 150 healthy controls in Taiwan was performed to explore the association between NAT2 genetic polymorphism and individual susceptibility to breast cancer. A structured questionnaire was used to collect relevant information regarding all known or suspected risk factors of breast cancer. The NAT2 genotype was determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 139 cases and 133 controls, and 28.8% and 21.1%, respectively, were found to have slow acetylator genotypes. Multivariate analysis, simultaneously considering other risk factors, including age at menarche, nulliparity or age at first full-term pregnancy, body mass index (BMI), hormone replacement therapy (HRT) and smoking status, showed that the NAT2 slow acetylator genotype was associated with an increased risk with borderline significance (Odds Ratio, 1.81; 95% CI, 1.01-3.31). Interestingly, this association was not significant in premenopausal women, but was significant in post-menopausal women. Further stratification of our study subjects based on different risk factor status showed that the increased risk for an NAT2 slow acetylator was more marked in post-menopausal women who were not using HRT or who had a lower BMI. Our findings suggest that NAT2 polymorphism is a susceptibility factor for breast cancer in Taiwanese women, and that NAT2-metabolized carcinogens are probably present in the environment and may be associated with induction of breast cancer.

Acetylation↗
PubMed2005

[Association of genetic polymorphism of XRCC1 with susceptibility to acute childhood leukemia].

OBJECTIVE: To explore the association between genetic polymorphisms of XRCC1 and susceptibility to acute childhood leukemia. METHODS: A case-control study with 63 childhood leukemia patients and 66 control subjects was conducted to investigate the role of three XRCC1 polymorphisms (c. 194, c. 280 and c. 399 ) on susceptibility to childhood leukemia. Genotyping was performed using Polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) to detect the single nucleotide polymorphisms (SNPs) of XRCC1 gene. RESULTS: There was a 2.235-fold increased risk of childhood leukemia for individuals carrying XRCC1c. 399 Gin allele (95% CI 1.038 - 4.812) compared with subjects carrying Arg/Arg allele, and the OR among boys was 3.110 (95% CI 1.235 - 7.831). No interaction was found between X-ray exposure and XRCC1 polymorphisms using Logistic regression analysis. CONCLUSION: Polymorphism of XRCC1 gene may contribute to the higher risk of childhood leukemia.

Acute Disease↗
PubMed1999

Implications of certain genetic polymorphisms in scarring in vesicoureteric reflux: importance of ACE polymorphism.

Polymorphisms of the renin-angiotensin system (RAS) have been shown to affect renal prognosis in a number of diseases. We examined the influence of deletion (D) and insertion (I) polymorphism in the angiotensin I-converting enzyme (ACE) gene and the other polymorphic markers of RAS, and that of plasminogen-activator inhibitor-1 (PAI-1) on renal scarring in reflux nephropathy. Ninety-four children with third- or fourth-degree reflux were the subject of the study. They were stratified into two groups according to the technetium-99m-dimercaptosuccinic acid (DMSA) findings: the first group consisted of 41 patients with no scar formation. In the second group (n = 53), there was significant scar formation in the refluxing units. ACE levels, ACE gene, angiotensin-1 receptor (AT1) A1166C, angiotensinogen (ATG) M235T, and PAI-1 4G/5G polymorphisms were studied. In the second group with scarred kidneys, 18 patients had decreased renal function. The frequency of patients homozygous for the D allele was significantly greater in the second group with scar formation in the refluxing units compared with the first group of patients (P < 0.005). On multivariate analysis, the DD genotype was the only factor that had a significant impact on renal scar formation, introducing a 4.9-fold risk (P < 0.05, 95% confidence interval). We were unable to find any correlation with the presence ofDD genotype and hypertension, decreased renal function, proteinuria, or sex of the patient. DDgenotype correlated with the serum ACE levels (P < 0.005). AT1and ATGpolymorphisms and PAI-1 polymorphism did not correlate with scar formation or any of the parameters. This study provides evidence that the DDgenotype of ACE may be a genetic susceptibility factor contributing to adverse renal prognosis in reflux nephropathy; namely, scar formation. The role of the synergism between the aforementioned genetic polymorphisms can be enlightened with larger patient groups, possibly through multicenter studies.

Angiotensinogen↗