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PubMed1995

Structure and DNA sequence of the mouse MnSOD gene.

Oxidative damage to the cell has been implicated in the pathogenesis of a number of disorders, including chronic inflammation, aging, and cancer. Manganese superoxide dismutase (Mn-SOD) plays a major role in the protection of the mitochondrion from oxidative damage due to superoxide radicals and other excited oxygen species. In this report we describe the genomic organization and DNA sequence of the murine MnSOD gene. This gene is interrupted by four introns. The coding sequence of this gene was examined in C57BL/6J and C3H/HeJ mice that are SUSCEPTIBLE AND RESISTANT, respectively, to the pulmonary injuries induced by the inhaled oxidants, ozone, and hyperoxia. Since the predicted amino acid sequence for MnSOD does not differ for these strains, nor does the size or steady-state level of this transcript, biologic variability in the pulmonary inflammatory response to ozone and hyperoxia does not arise from an altered gene structure. Examination of the noncoding sequence revealed a dC.dA polymorphism in intron 2 and a StyI RFLV in intron 4 of the MnSOD gene. These sequence and mapping data provide the basis for continued study of biologic variability in the MnSOD gene as a cause of disease.

Amino Acid Sequence↗

PubMed2005

Intron 1 of the interferon gamma gene: Its role in nematode resistance in Suffolk and Texel sheep breeds.

Genetic variation at intron 1 of the interferon gamma gene has recently been associated with variation in faecal egg count in Romney, Merino and Soay breeds of sheep. The Texel breed is more resistant to gastrointestinal nematode infection than the Suffolk breed, based on faecal egg count. Hence, the objective of this experiment was to characterise the polymorphisms of intron 1 of the interferon gammagene in Suffolk and Texel sheep, and to determine if the characterised haplotype variants were associated with faecal egg count variation in these breeds. Intron 1 haplotypes and faecal egg measurements were determined for Suffolks (n=113) and Texels (n=135). Four haplotypes were identified in Suffolks (A, B, C and D), two haplotypes as previously described, and two previously unknown haplotypes. However, there was no association between interferon gamma intron 1 haplotype and faecal egg count in Suffolks. In contrast, two previously identified haplotypes (A and B) were present in the Texel breed, and the B haplotype was associated with resistance to nematode infection (P=0.02). These results suggest that intron 1 of the interferon gamma gene has an important role in resistance to nematode infection in the Texel breed.

Animals↗

PubMed2001

Variation at the Angiotensin-converting enzyme and endothelial nitric oxide synthase genes is associated with the risk of esophageal varices among patients with alcoholic cirrhosis.

Esophageal varices are a frequent complication among patients with liver cirrhosis. Nitric oxide and other vasoactive molecules regulate the vascular tone in both the liver microcirculation and the systemic and splanchnic circulation. Several genes that encode proteins involved in the maintenance of vascular tone, such as the endothelial-constitutive nitric oxide synthase (ecNOS), the angiotensinogen (AGT), the angiotensin-converting enzyme (ACE), and the angiotensin II receptor type 1 (AT1R) are polymorphic, and these polymorphisms have been associated with several cardiovascular diseases. Our aim was to define a possible role for DNA polymorphisms at these genes in the risk of developing esophageal varices among patients with alcoholic cirrhosis. We analyzed 145 male patients with liver cirrhosis. Patients and 200 healthy controls were genotyped by polymerase chain reaction for the ACE-I/D, the AGT-M235T, the AT1R-A1166C, and the ecNOS-4/5 (intron 4) polymorphisms. Ninety-five patients had varices and 50 did not show this complication. Carriers of the ACE-I allele (ID + II genotypes) were at a significantly higher frequency among patients with varices (p = 0.013). Patients without varices had a higher frequency of the ecNOS-4 allele compared with patients with varices (p = 0.026). ACE-I carriers + ecNOS-55 were at a significantly higher frequency (p = 0.0012; odds ratio = 3.19; 95% CI = 1.55-6.55) among patients with varices (51 of 95, 54%) compared with patients without (18 of 50, 36%). Allele and genotype frequencies for the AGT and AT1R polymorphisms did not differ between the two groups. The genotypes associated with an increased risk for varices have been linked to higher plasma levels of nitric oxide and reduced levels of ACE. These genotypes could have a vasodilatory effect in the systemic and splanchnic circulation, thus favoring the development of portocollaterals.

Adult↗

PubMed1998

Mutation of the transforming growth factor-beta type II receptor gene is a rare event in human sporadic gastric carcinomas.

Mutations of the transforming growth factor-beta type II receptor (TGF-beta RII) gene have been detected in several human cancers. However, mutation analysis of coding sequences of TGF-beta RII in gastric carcinomas has not yet been fully elucidated. We performed PCR-SSCP analysis and direct DNA sequencing of the entire coding region of TGF- RII in 38 human sporadic gastric cancers and 8 gastric cancer cell lines. Mutations of the TGF-beta RII were detected in two tumors and three cell lines. Two tumors had one base deletion in the polyadenine tract in exon 3, the cystein-rich extracellular domain. Three cell lines had a silent mutation in the kinase domain located in exon 4. Polymorphisms were detected in introns 2 and 3. An a/g polymorphism was observed at the seventh base in intron 2 and an a/t polymorphism was observed at the fourth to last base in intron 3. There were no mutations in exons 1, 2, 5, 6 and 7. These results indicate that the polyadenine tract in the TGF-beta RII is a mutational hot spot in human gastric cancer. However, these results also suggest that mutations of the gene are rare events in human sporadic gastric cancer.

DNA Primers↗

PubMed1996

Deletion polymorphism in the angiotensin I converting enzyme (ACE) gene as a genetic risk factor for sarcoidosis.

BACKGROUND: Genetic control of serum angiotensin I converting enzyme (SACE) levels has been suggested. A study was undertaken to elucidate the role of this polymorphism in sarcoidosis. METHODS: Three hundred and forty one unrelated healthy controls and 103 consecutive patients with sarcoidosis participated in the study. SACE levels and an insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene were studied in each subject and new reference intervals for SACE activity for each genotype were determined. The difference in genotype and allele frequencies between controls and patients was analysed and odds ratios were calculated to estimate the relative risk. RESULTS: A significant association was seen between ACE gene polymorphism and SACE levels in both patients and controls. The new reference intervals for each genotype discriminated abnormal SACE levels in patients more accurately, especially those with genotype II. In women the frequencies of allele I were 0.68 (allele D 0.32) in controls and 0.58 (allele D 0.42) in patients, and the difference between the two female groups was significant (p < 0.05). Thus, an excess of genotype ID or DD was observed in female patients (odds ratio 2.18; 95% confidence interval 1.18 to 4.01; p = 0.01). CONCLUSIONS: These findings suggest that ACE gene polymorphism is associated with SACE levels in both patients with sarcoidosis and controls. ACE gene polymorphism should be further evaluated as a candidate marker for an increased risk of sarcoidosis.

Adult↗

PubMed1997

Phenotypic variation in patients heterozygous for familial defective apolipoprotein B (FDB) in three European countries.

A glutamine-for-arginine substitution at amino acid position 3500 of apolipoprotein B (apo B) causes synthesis of LDL with reduced binding affinity to the LDL receptor (LDLR). The associated clinical syndrome has been named familial defective apolipoprotein B- 100 (FDB). In 205 FDB patients from Germany (n = 73). The Netherlands (n = 87), and Denmark (n = 45), we tried to assess determinants of variation in lipid concentrations. Besides age, sex, and geographic origin, variation in the LDLR gene was the most powerful determinant of variation in total cholesterol and LDL cholesterol levels. Polymorphic variation in the LDLR gene (SfaNI, exon 2; Nco I, exon 18) was associated with total cholesterol (TC) and LDL cholesterol (LDL-C) variation in women (SfaNI: P = .04 and .03 for TC and LDL-C, respectively; Nco I; P = .003 and .006, respectively), whereas the Ava II (exon 13) and the Pvu II (intron 15) polymorphisms were not. Combined information from all three LDLR exon polymorphisms showed that subjects with at least one S + A + N + allele had 13% to 20% higher TC than non-S + A + N + subjects (P = .02 [TC, men]; P = .01 [LDL-C, men]; P = .005 [TC, women]; and P = .004 [LDL-C, women]) and, together with age and geographic origin, accounted for 20% (women) and 19% (men) of the variation in LDL-C. The expected association of the apo E genotypes (e3e2, e3e3, and e3e4) with cholesterol concentrations was seen in S + A + N + but not in non-S + A + N + subjects and in P-P- but not in P + P + or P + P- subjects. With regard to clinical expression, FDB patients had lower TC and LDL-C levels and a lower prevalence of cardiovascular disease than 101 Danish patients with familial hypercholesterolemia.

Adult↗

PubMed2002

Haplotype-specific effects on endothelial NO synthase promoter efficiency: modifiable by cigarette smoking.

The T-786C promoter and 27-bp repeat intron 4 polymorphisms in the endothelial NO synthase (eNOS) gene have been inconsistently associated with various eNOS-related phenotypic changes. We explored molecular mechanisms underlying the inconsistency. We constructed pGL3 luciferase reporter vectors by inserting an eNOS promoter fragment containing either T or C nucleotide at -786 bp at the 5' end of the luciferase coding region and eNOS intron 4 containing either 5x or 4x27-bp repeats at the 3' end of the luciferase gene. The transcription efficiency in the T promoter was lower than in the C promoter (15.7+/-1.0% vs 83.3+/-5.8%, P<0.01 when 5x27-bp was an enhancer and 37.6+/-4.7% vs 58.9+/-7.5%, P<0.01 when 4x27bp was an enhancer). Although cigarette smoking extracts treatment increased the transcription efficiency significantly in the T promoter (1.7-fold, P<0.01), it reduced the C promoter efficiency (by 10% to 15%). A mobility shift assay revealed positive binding of the 27-bp repeat fragment with endothelial cell nuclear protein extracts. Our study demonstrates a cis-acting role of the 27-bp repeats in eNOS promoter function and a haplotype-specific expression pattern determined by DNA variants at -786 bp and intron 4 of the eNOS gene that is also modifiable by cigarette smoking.

Cell Line↗

PubMed1997

Human XPMC2H: cDNA cloning, mapping to 9q34, genomic structure, and evaluation as TSC1.

XPMC2 is a Xenopus gene identified on the basis of its ability to correct a mitotic defect in fission yeast. Here we report the identification of cDNA clones for human XPMC2H, its mapping to the tuberous sclerosis gene TSC1 region on 9q34, determination of genomic structure, and identification of several coding region polymorphisms. The predicted protein has strong sequence similarity to the Xenopus gene. Through SSCP and heteroduplex analysis of genomic DNA, we found two intragenic polymorphisms but no evidence for significant mutations in patients with tuberous sclerosis in this gene.

Chromosome Mapping↗

PubMed2003

Extensive polymorphism and different evolutionary patterns of intron 2 were identified in the HLA-DQB1 gene.

Exon 2 and intron 2 of the HLA DQB1 gene from 20 individuals were cloned and sequenced and eight alleles were obtained. Based on our analysis, the nucleotide diversity of the 5' end of intron 2 was higher than the synonymous nucleotide diversity of exon 2, which may be due to the lower GC content and the 'hitch-hiking effect'. In contrast, the opposite phenomenon was observed for the 3' end of intron 2, which may be the result of the recombination between the 3' end and 5' end of intron 2 and the subsequent genetic drift. The results indicated that different regions of intron 2 in the DQB1 gene had different evolutionary patterns.

Alleles↗

PubMed2003

Association study of serotonin transporter gene VNTR polymorphism and mood disorders, onset age and suicide attempts in a Chinese sample.

The human serotonin transporter (5-HTT) gene is an important candidate for the pathogenesis of mood disorders. Associations have been reported between a variable-number tandem-repeat polymorphism in intron 2 of the serotonin transporter gene (5-HTTVNTR) and mood disorders in a number of studies of Western and Chinese populations. However, no such relationships have been determined in other analogous research. To replicate these positive findings in a Chinese population and to determine the association between onset age of bipolar disorder and 5-HTTVNTR, we investigated the prevalence of this polymorphism in an independent Chinese population (83 bipolar disorder patients, 77 major depressive disorder patients and 169 controls), demonstrating no significant association between the 5-HTTVNTR polymorphism and mood disorders or age at onset. Further, no association was demonstrated between this polymorphism and suicidal history in mood disorder patients. These negative findings suggest that 5-HTTVNTR does not play a major role in the pathogenesis of mood disorder in Chinese populations.

Adult↗

PubMed2005

Association of oestrogen receptor alpha gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone.

BACKGROUND: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk. OBJECTIVE: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women. RESULTS: There was a significant association between a common haplotype "px", defined by the PvuII and XbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n = 945; p = 0.009). Annual rates of femoral neck bone loss were approximately 14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p = 0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p = 0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values. CONCLUSIONS: The ESR1px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD.

Alleles↗

PubMed2004

Increased amount of the angiotensin-converting enzyme (ACE) mRNA originating from the ACE allele with deletion.

The insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene is involved in the development of cardiovascular diseases. We compared the ACE mRNA expression originating from the allele with a deletion (D allele) and that from the allele with an insertion (I allele) in human white blood cells from ID heterozygotes. We identified the mRNA from the I allele by using the G2215A polymorphism that lies in exon 15 and that was linked to the I/D polymorphism. RNA samples were obtained from 12 healthy heterozygotes of both I/D and G2215A, and every insertion was shown to be linked to 2215G. ACE mRNA was amplified by the reverse transcription/polymerase chain reaction (RT-PCR) method with an end-labeled antisense primer. The PCR products were digested with HaeII and separated by electrophoresis, and the relative radioactivities of the 2215A and 2215G bands were measured on an auto-image analyzer. The results showed that, in every cases, the intensity of the 2215A product (D allele origin) was higher than that of the 2215G product (I allele origin). The mean ratio of 2215A to 2215G was 1.79 (1.11-2.62). Thus, the D allele leads to higher expression of the ACE mRNA and may affect the renin-angiotensin system in local regions.

Adult↗

PubMed2000

Fine mapping of the human preprocortistatin gene (CORT) to neuroblastoma consensus deletion region 1p36.3-->p36.2, but absence of mutations in primary tumors.

The processed product of the human gene preprocortistatin, the peptide cortistatin-17 (hCST-17), bears a strong structural resemblance to the peptide somatostatin (SST), which has an identical receptor binding domain. CST has affinity to all known SST receptor (SSTR) subtypes. Expression of both SST and its receptors has been shown in previous studies to have biological and clinical significance in neuroblastomas, with a putative role in tumor differentiation and apoptosis in vivo. In this work we have employed radiation hybrid mapping and BAC physical mapping to map the human preprocortistatin gene (CORT) to chromosome region 1p36.3-->p36.2, close to the genetic marker D1S244. D1S244 defines the centromeric border of the smallest region of overlap of deletion in our primary neuroblastoma material. We have also defined the genomic sequence of the gene by BAC sequencing and found that preprocortistatin consists of two exons divided by a 1-kb intron. Two polymorphic sites, neither of which causes amino acid exchange, have been detected in the coding region of the gene. Expression studies showed that preprocortistatin is expressed in neuroblastomas of all different stages, as well as in ganglioneuromas. Through genomic sequencing we made mutation analyses of exonic sequences in 49 primary neuroblastomas of all different stages, but no mutations could be detected.

Base Sequence↗

PubMed2004

Polymorphisms of dopamine degradation enzyme (COMT and MAO) genes and tardive dyskinesia in patients with schizophrenia.

Several lines of evidence suggest that tardive dyskinesia (TD) may be associated with altered dopaminergic neurotransmission. We hypothesized that deranged dopamine degradation enzyme activities might be related to the susceptibility to TD through altered dopaminergic neurotransmission in the central nervous system. In the present study, we investigated the relationship between the gene polymorphisms of three dopamine degradation enzymes and TD. We genotyped the valine/methionine polymorphism of codon 108/158 in the catechol-O-methyltransferase (COMT) gene, the 30-bp repeat polymorphism in the promoter of the monoamine oxidase A (MAOA) gene, and the A/G polymorphism in intron 13 of the monoamine oxidase B (MAOB) gene in 206 Japanese patients with schizophrenia. No significant difference was found in total scores on the Abnormal Involuntary Movement Scale (AIMS) among the subject groups, sorted according to the COMT, MAOA and MAOB genotypes. Moreover, no significant difference was found in allele frequencies between patients with TD and patients without TD for any of the polymorphisms. As both COMT and MAO genes are involved in degrading catecholamines, we also sought evidence for additive and epistatic effects, but none was observed. Our data, therefore, do not support the hypothesis that polymorphisms in COMT, MAOA, and MAOB genes are involved individually or in combination in the predisposition to TD.

Antipsychotic Agents↗

PubMed2002

Endothelial nitric oxide synthase affects the progression of autosomal dominant polycystic kidney disease.

BACKGROUND/AIM: The phenotypic variability of autosomal dominant polycystic kidney disease (ADPKD) cannot be explained only by various mutations of two known genes (PKD1 and PKD2), but the influence of other unknown factors should also be considered. Impairment of endothelial function has been observed in ADPKD patients. Our study tried to verify the hypothesis that endothelial nitric oxide synthase (ecNOS) gene polymorphisms in intron 4 could have some relevance to the progression of ADPKD. METHODS: We examined 155 Czech patients with ADPKD (80 males, 75 females; mean age 43.4 +/- 14.7 years) and 100 genetically unrelated healthy subjects (50 men, 50 women; mean age 51.2 +/- 8.2 years). The genomic DNA was amplified by polymerase chain reaction and the products were separated on 1.5% agarose gel and visualised by ultraviolet transillumination. We compared subjects homozygous for the ecNOSb allele with subjects homozygous and heterozygous for the ecNOSa allele. RESULTS: The frequencies of ecNOSb/b, ecNOSa/b and ecNOSa/a were 81% (81/100), 17% (17/100) and 2% (2/100), respectively, in the control group, 60% (30/50), 32% (16/50) and 8% (4/50), respectively, in ADPKD patients with end-stage renal failure (ESRF), and 68.5% (72/105), 28.6% (30/105) and 2.9% (3/105), respectively, in ADPKD patients with normal renal function. The two-tailed t test revealed that the frequency of the ecNOSa allele (ecNOSa/b and ecNOSa/a) in dialysed patients was significantly higher than in ADPKD patients with normal renal function (p < 0.05). CONCLUSION: The a allele of the ecNOS gene polymorphism showed a significantly higher incidence among patients with ESRF caused by ADPKD. The a allele might have a negative influence on the progression of ADPKD.

Adult↗

PubMed2001

Gene variants of the bactericidal/permeability increasing protein and lipopolysaccharide binding protein in sepsis patients: gender-specific genetic predisposition to sepsis.

OBJECTIVES: To determine whether the genotype frequencies of the five bi-allelic polymorphisms in the bactericidal/permeability increasing protein (BPI) (Lys216 --> Glu; PstI polymorphism in intron 5; silent mutation G545 --> C) and the lipopolysaccharide binding protein (LBP) (Cys98 --> Gly; Pro436 --> Leu) are associated with the incidence and lethality of sepsis. DESIGN: Case control study of patients with sepsis. SETTING: Intensive care units within university hospitals. PATIENTS: A total of 204 patients diagnosed with sepsis and 250 healthy blood donors. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Short DNA fragments containing the polymorphic sites of the LBP and BPI locus were amplified by the polymerase chain reaction or mismatched polymerase chain reaction. The individual polymorphisms were determined with the appropriate restriction enzyme digestions and subsequent agarose gel electrophoresis. The presence of LBP genotypes with the less frequent Gly98 allele was found to be associated with sepsis (p < .02) in male patients, but not in females. Patients which were homozygote for either of the rare Gly98 (n = 6) and/or Leu436 (n = 5) LBP alleles, furthermore, exclusively were nonsurvivors of sepsis. The genotype frequencies in the BPI gene did not differ between patients and control individuals. CONCLUSIONS: Our findings suggest that common polymorphisms in the gene for LBP in combination with male gender are associated with an increased risk for the development of sepsis and, furthermore, may be linked to an unfavorable outcome. These data support the important immunomodulatory role of LBP in Gram-negative sepsis and suggest that genetic testing may be helpful for the identification of patients with an unfavorable response to Gram-negative infection.

Acute-Phase Proteins↗

PubMed2002

[Interleukin (IL)-1beta, IL-1 receptor antagonist and IL-4 gene polymorphisms in ulcerative colitis in the Chinese].

OBJECTIVE: To study whether the Chinese ulcerative colitis (UC) patients are associated with interleukin (IL)-1beta, IL-1RA and IL-4 gene polymorphisms and to analyze the relationship among gene polymorphisms, antineutrophil cytoplasmic antibodies (ANCA) and clinical classification of UC. METHODS: eighty-one UC patients and 114 healthy subjects (HS) were enrolled. IL-1beta, IL-1RA, and IL-4 gene polymorphisms were analyzed with polymerase chain reaction-restriction fragment length polymorphism and polymerase chain reaction with sequence-specific primers respectively. RESULTS: The gene frequency of allele RP2 of IL-4 in UC patients was significantly higher than that in HS (29.0% vs 11.8%, P = 0.00002), but the gene frequency of allele RP1 in HS was significantly higher than that in UC patients (88.2% vs 71.0%, P = 0.00002). OR of the genotype RP1.2 and RP2.2 were 2.71 (95% CI 1.39 approximately 5.31) and 9.04 (95% CI 1.05 approximately 203.29) respectively. There was not difference in the gene frequencies of IL-1beta, IL-1RA between UC patients and HS (P > 0.05). When UC patients were divided into ANCA positive and negative groups, it was found that there was significant difference in the gene frequencies of allele RP1, RP2 of IL-4 between two groups (63.7% vs 83.3%, 36.3% vs 16.7%, P < 0.05). CONCLUSIONS: There is correlation between the Chinese UC patients and the gene polymorphisms of intron 3 of IL-4. The gene frequency of allele RP1 in UC patients are lower, but the gene frequency of allele RP2 is significantly higher. The differences on gene frequencies of IL-4 between the UC patients and HS are mainly found in the ANCA positive UC patients. The Chinese UC patients are not associated with IL-1beta and IL-1RA gene polymorphisms.

Adult↗

PubMed1997

Associations between candidate loci angiotensin-converting enzyme and angiotensinogen with coronary heart disease and myocardial infarction: the NHLBI Family Heart Study.

Angiotensin-converting enzyme (ACE) and angiotensinogen (AGT) are major components of the renin-angiotensin systems. An association between myocardial infarction (MI) and the ACE DD genotype of the insertion/deletion (ID) polymorphism in intron 16 of the ACE gene has been reported. However, other similarly designed studies have not found such an association. Angiotensin II, the product of AGT, has a direct effect on vascular tone; and a variant in the AGT gene has been found to be associated with MI in the Japanese. This case-control study was initiated to investigate whether the ACEI/D and AGT M235T polymorphisms are associated with an increased risk for coronary heart disease (CHD) and MI. Our study groups were composed of participants in the National Heart Lung Blood Institute (NHLBI) Family Heart Study (FHS) selected from three population-based studies: two Atherosclerosis Risk in Communities (ARIC) centers (Forsyth County, NC, and Minneapolis, MN), and the Framingham Heart Study. In multivariate analysis within ARIC Caucasians, a significant positive association was found between CHD (controls = 230, cases = 232) and the AGT TT genotype (P = 0.022; OR = 1.84, 1.09-3.10 95% CI). When we restricted the analysis to a low-risk group for CHD (controls = 70, cases = 35) an interaction between the ACE DD and AGT TT genotypes was significant (P = 0.025; OR = 5.02 1.22-20.6 95% CI). After further subsetting low-risk cases to those with a definite MI (controls = 74, cases = 16), we found that the associations with the ACE DD genotype was also significant (P = 0.013, OR = 3.94, 1.28-12.2 95% CI). Comparable tests in the Framingham sample failed to support an association of these markers with CHD. In conclusion, within selected groups the ACE D and AGT 235T alleles are statistically associated with CHD and MI, and there is a synergistic interaction between the two alleles. These results and those from previous studies together suggest that the association of these two loci is neither strong nor consistent and involves a complex interaction among risk factors and genotypes.

Angiotensinogen↗