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Biomedical subjects

W Renner

Publications and source records attributed to W Renner.

At least 19 recordsLinked to original sources
PubMed2006

Adult-type hypolactasia and calcium availability: decreased calcium intake or impaired calcium absorption?

UNLABELLED: Adult-type hypolactasia, as mediated by a widespread genetic predisposition, not only reduces calcium intake but also calcium absorption in the presence of high amounts of lactose and may, therefore, promote osteoporosis. A lactose-reduced diet and lactose-free calcium supplements may reverse this imbalance. INTRODUCTION AND HYPOTHESIS: Adult-type hypolactasia (HL) defined by the LCT(-13910) polymorphism may reduce calcium intake by reducing dairy consumption and, therefore, promote osteoporosis. This study aimed to evaluate whether lactose also decreases intestinal calcium absorption in subjects with HL and whether lactose-reduced diet and lactose-free calcium supplementation as recommended could maintain bone mineral density (BMD). METHODS: Based on LCT genotyping, 73 postmenopausal women with and without HL underwent a conventional H(2) breath test with a concomitant oral strontium absorption test lasting 150 minutes, which closely reflects intestinal calcium absorption. In addition, we compared bone-specific laboratory parameters, lumbar and femoral BMD, and spinal radiographs to a similar bone assessment 5 years earlier. RESULTS: LCT genotyping and functional lactose malabsorption tests were highly correlated. Dairy product consumption was reduced by 80% in HL individuals. During concomitant lactose application, mean strontium absorption was blunted by 54% in HL subjects after 150 minutes (1272 +/- 629 microg/L vs. 2020 +/- 1130 microg/L in lactose tolerant subjects, p=0.001). Nevertheless, BMD in HL subjects remained stable with lactose-free calcium supplements during the observation period. CONCLUSION: Both decreased calcium intake as well as lactose-associated impaired calcium absorption may predispose subjects with HL to osteoporosis. Lactose-free calcium supplementation may help to maintain BMD in HL subjects.

Absorption↗
PubMed2006

The serotonin transporter gene polymorphism is not associated with smoking behavior.

Nicotine increases serotonin release in the brain and symptoms of nicotine withdrawal may be modulated by diminished serotonergic neurotransmission. The promoter region of the serotonin transporter gene, solute carrier family neurotransmitter transporter member 4 (SLC6A4), contains a functional tandem repeat polymorphism. The long (L) variant is more actively transcribed than the short (S) variant and is associated with a higher serotonin uptake. To investigate the potential role of this polymorphism for smoking behavior, SLC6A4 genotypes were determined in two different studies, the SMOKING GENES case-control study (470 current smokers and 419 subjects who had never smoked) and the cross-sectional Ludwigshafen risk and cardiovascular health (LURIC) study (777 current smokers and 1178 subjects who had never smoked). In the SMOKING GENES case-control study, SLC6A4 genotype frequencies were not statistically different between smokers (LL: 30.9%; LS: 46.8%; SS: 16.4%) and non-smokers (LL: 36.3%; LS: 41.8%; SS: 14.3%; P=0.13). Similar results were obtained in the cross-sectional LURIC study (smokers: LL, 36.5%, LS, 45.6%, SS, 17.9%; non-smokers: LL, 33.6%, LS, 48.9%, SS, 17.6%; P=0.33). SLC6A4 genotypes were furthermore not associated with Fagerstrom Tolerance Questionnaire score, packyears, number of cigarettes smoked per day or previous attempts to quit smoking. We conclude that the SLC6A4 promoter polymorphism is not a major determinant of smoking behavior in Caucasian.

Adult↗
PubMed2005

TNF-alpha promoter polymorphisms and primary open-angle glaucoma.

PURPOSE: Primary open-angle glaucoma (POAG) is a multifactorial optic neuropathy with a strong hereditary component. Recent studies suggested a role for tumour necrosis factor-alpha(TNF-alpha) in the pathogenesis of POAG. The purpose of the present study was to investigate a hypothesized association between the TNF-alpha-308G>A and -238G>A gene polymorphisms and the presence of POAG in a Caucasian population. METHODS: The present case-control study comprised 114 unrelated patients with POAG and 228 healthy control subjects, matched for age and gender. Genotyping of the TNF-alpha-308G>A and -238G>A polymorphisms was performed using polymerase chain reaction. RESULTS: Allelic frequencies and genotype distributions of both the TNF-alpha-308G>A and -238G>A gene polymorphisms did not significantly differ between patients with POAG and control subjects. Presence of the TNF-alpha-308A-allele was associated with an odds ratio (OR) of 0.96 for POAG, whereas an OR of 0.52 was found among carriers of the TNF-alpha-238A-allele. CONCLUSION: Our data suggest that none of the investigated TNF-alphagene polymorphisms is a major risk factor among Caucasian patients with POAG.

Aged↗
PubMed2004

Diminished response to activated protein C is not correlated with severity of peripheral arterial occlusive disease.

INTRODUCTION: Poor response to activated Protein C (APC) is a well established risk factor for venous thromboembolism. More recently, the hypercoagulable state which results from diminished response to APC has also been associated with arterial thrombosis. Some studies showed a clear association between low response to APC with advanced arterial disease, others, however, failed to support these data. Thus, there is ongoing dispute about the impact of a hypercoagulable state upon progression of atherosclerosis. MATERIAL AND METHODS: We investigated APC ratios and the existence of Factor V Leiden in 800 patients with documented peripheral arterial occlusive disease (PAD). Clinical symptoms according to Fontaine stages II (intermittent claudication), III (rest pain) and IV (gangrene) and the ankle/brachial index served as parameters for the severity of PAD. RESULTS: There was no association between low response to APC or existence of Factor V Leiden and the clinical stage of PAD or ankle/ brachial index. CONCLUSION: Our data suggest that poor response to APC is not correlated with the severity of peripheral arterial occlusive disease.

Activated Protein C Resistance↗
PubMed2003

Role of factor V Leiden and prothrombin 20210A in patients with retinal artery occlusion.

PURPOSE: Retinal artery occlusion is a common vision-threatening disease. Among other risk factors, coagulopathies leading to a hypercoagulable state have been associated with retinal artery occlusion. Numerous studies have shown that two genetic variants, factor V Leiden and prothrombin 20210A, cause a procoagulant state. However, their role in the pathogenesis of retinal artery occlusion is still unclear. The purpose of the present study was therefore to investigate a possible association between factor V Leiden, prothrombin 20210A, and retinal artery occlusion. METHODS: In the present retrospective case-control study, we studied 136 patients with retinal artery occlusion and 136 age- and gender-matched control subjects. The presence of factor V Leiden and prothrombin 20210A alleles was determined by polymerase chain reaction. RESULTS: The prevalence of heterozygosity for the prothrombin G20210A variant did not significantly differ between patients and controls (three patients vs two controls, P=0.65). Distribution of factor V Leiden genotypes revealed no significant difference among the two groups (heterozygosity: eight patients vs 11 controls, P=0.47). As for other risk factors, arterial hypertension, a history of stroke and myocardial infarction were significantly more frequent in patients than in controls. CONCLUSION: Our data suggest that factor V Leiden and prothrombin 20210A do not play a major role in patients with retinal artery occlusion.

Adult↗
PubMed2003

Lack of association of the Glu298Asp polymorphism of endothelial nitric oxide synthase with manifest coronary artery disease, carotid atherosclerosis and forearm vascular reactivity in two Austrian populations.

OBJECTIVE: Conflicting data exists about the possible contribution of the homozygous Asp/Asp genotype of the Glu298Asp polymorphism of endothelial nitric oxide synthase to human atherosclerotic vascular disease. We investigated the polymorphism in two independent study populations: a case-control study including patients with angiographically verified coronary artery disease (CAD) on the one hand and a cross-sectional epidemiological study on the other hand. METHODS: The Glu298Asp polymorphism was determined by PCR-RFLP as established. In the case-control study (240 patients and 248 controls) a possible association between the polymorphism and CAD, and age of onset of CAD and myocardial infarction was investigated. In the cross-sectional epidemiological study (932 subjects) intima-media thickness (IMT) of the carotid artery as well as morphological plaque burden and forearm vascular reactivity (peak postischemic reactive hyperaemia, determined by venous occlusion plethysmography) were measured. RESULTS: In the case-control study genotype distribution (Glu/Glu; Glu/Asp; Asp/Asp) was not different between the CAD patients (43/46/11%) and the controls (49/41/10%, P = NS). No association of the polymorphism with age of onset of CAD or myocardial infarction was found. In the epidemiological study no influence of the genetic variant on IMT was observed after correction for classical determinants of IMT (average IMT: Asp/ Asp: 0.077 +/- 0.011 mm; Glu/Glu and Glu/Asp: 0.080 +/- 0.012 mm, P = NS). Forearm vascular reactivity was also not different between homozygous Asp/Asp subjects and Glu/Glu and Glu/Asp subjects (peak-reactive hyperaemia 20.1 +/- 7.3 mL min-1 100 mL-1 vs. 20.0 +/- 6.5 mL min-1 100 mL-1, P = NS). CONCLUSIONS: Our results suggest that there is no association of the Glu298Asp polymorphism with coronary or carotid atherosclerosis or forearm vascular reactivity in these populations recruited in a country with a rather high risk for atherosclerosis. We suggest additional investigations to be performed in populations at different risk for coronary events to further elucidate the possible contribution of this polymorphism to vascular disease.

Adult↗
PubMed2002

G-455A polymorphism of the fibrinogen beta gene and deep vein thrombosis.

BACKGROUND: Elevated fibrinogen levels have been linked to increased risk for deep venous thrombosis, although it is not clear whether fibrinogen is causal or rather a marker for the presence of other risk factors. A common G/A polymorphism in the gene for the fibrinogen beta-chain (FGB G-455A) is associated with elevated fibrinogen levels. The present study was designed to analyze the role of this genetic marker for deep venous thrombosis. MATERIALS AND METHODS: We performed a case-control study including 307 patients with documented deep venous thrombosis and 316 control subjects. beta-fibrinogen genotypes were determined by allele-specific polymerase chain reaction. RESULTS: GG, GA and AA genotype frequencies were similar among the patients (53.1%, 41.0, 5.9) and controls (51.6%, 42.1, 6.3; P = 0.92). Fibrinogen levels of the patients (median 3.72 g l-1; range 1.93-11.6) did not differ significantly from those of the controls (3.76; 2.17-9.99). Carriers of the homozygous AA genotype had significantly higher fibrinogen levels than noncarriers (patients: 5.32 vs. 3.59; P = 0.024; controls: 6.29 vs. 3.72; P = 0.048). CONCLUSION: Our data suggest that the fibrinogen-elevating FGB G-455A gene polymorphism is not linked to an increased risk for deep venous thrombosis.

Alleles↗
PubMed2002

The V34L polymorphism of factor XIII and peripheral arterial disease.

BACKGROUND: Factor XIII catalyzes crosslinking of fibrin in the last steps of the coagulation process. A common polymorphism in the gene for factor XIII A subunit (F13A1 V34L) has been associated with a decreased risk for coronary artery disease, cerebrovascular disease, and deep venous thrombosis. METHODS: To analyze the role of this polymorphism in peripheral arterial disease (PAD) we performed a case-control study including 873 patients with documented PAD and a total of 523 controls without vascular disease. The F13A1 genotype was determined by an allele-specific polymerase chain reaction. RESULTS: Genotype distribution and allele frequencies were not significantly different between patients (VV: 51.9%; VL: 40.7%; LL: 7.4%) and controls (VV: 54.7%; VL: 39.2%; LL: 6.1%). Mean age at onset of the disease was significantly higher in LL homozygous subjects than in VV homozygous subjects (67.3 versus 64.1 years, p=0.017). Heterozygous subjects had an intermediate age at onset (65.1 years), suggesting a gene-dose effect. The association of the L34 variant with onset of PAD remained significant after adjustment for other risk factors. The effect was stronger in men than in women. CONCLUSIONS: We conclude that the F13A1 V34L polymorphism was not associated with the presence of PAD in our study, but may be linked to a later onset of the disease.

Aged↗
PubMed2002

Genetic evaluation of the common variant of the endothelial nitric oxide synthase (Glu(298)-><Asp) in patients with thromboangiitis obliterans.

BACKGROUND: Nitric oxide is synthesized by endothelial nitric oxide synthase and plays a key role in adequate endothelial function. An important effect is the reduction of free radicals caused by cigarette smoking, which is the only established risk factor for thromboangiitis obliterans (TAO). In patients with TAO a genetic defect of endothelial nitric oxide synthase may therefore result in deteriorated endothelial function. The aim of our study was to evaluate whether a genetic defect of the common variant of endothelial nitric oxide synthase (Glu(298)-->Asp) can be found in a higher degree in patients with TAO compared to healthy controls. METHODS: We enrolled 42 patients with TAO and 149 healthy subjects. RESULTS: Nineteen patients (45.2%) showed homozygosity for Glu(298) versus 76 (51%) in the control group. The heterozygous status for Glu(298)-->Asp was found among 18 patients (42.9%) compared to 61 (40.9%) members of the control group, which was a nearly equal distribution. Homozygosity for the mutant Asp(298) was slightly elevated in the patient group with 11.9 versus 8.1% in the control group. Allele frequency for Asp(298) was 0.333. CONCLUSIONS: Our data do not show elevated homozygosity for the common variant Glu(298)-->Asp in patients with TAO compared to healthy controls. The limitation of our evaluation is the small number of patients, which is a general problem when evaluating patients with TAO, as this is not a common disease.

Aspartic Acid↗
PubMed2001

Role of factor XIII Val34Leu polymorphism in retinal artery occlusion.

BACKGROUND AND PURPOSE: Factor XIII (FXIII) Val34Leu, a common polymorphism in the gene for factor XIII, has been associated with a lower risk of stroke, myocardial infarction, and deep vein thrombosis. Ineffective fibrin cross-linking has been suggested to be causative. The aim of the present case-control study was to investigate the role of FXIII Val34Leu polymorphism in patients with retinal artery occlusion. METHODS: A total of 108 patients with retinal artery occlusion and 313 age- and sex-matched controls were genotyped for the FXIII Val34Leu polymorphism. Factor XIII Val34Leu genotypes were determined by use of allele-specific polymerase chain reaction. RESULTS: Homozygous Leu genotype was found significantly more often in control subjects than in patients with retinal artery occlusion (P=0.018), with an odds ratio of 0.22 (95% confidence interval 0.07 to 0.74). Distribution of the Val/Val and Val/Leu genotypes did not differ significantly between groups. CONCLUSIONS: Because prevalence of homozygous Leu genotype was significantly higher in controls, we conclude that the Leu/Leu genotype is associated with a protective effect against retinal artery occlusion.

Adult↗
PubMed2001

A high-throughput alphavirus-based expression cloning system for mammalian cells.

We have developed a widely applicable functional genomics strategy based on alphavirus expression vectors. The technology allows for rapid identification of genes encoding a functional activity such as binding of a defined ligand. Complementary DNA (cDNA) libraries were expressed in mammalian cells following infection with recombinant Sindbis virus (SIN replicon particles), a member of the Alphavirus genus. Virus-infected cells that specifically bound a ligand of choice were isolated using fluorescence-activated cell sorting (FACS). Replication-competent, infective SIN replicon particles harboring the corresponding cDNA were amplified in a next step. Within one round of selection, viral clones encoding proteins recognized by monoclonal antibodies or Fc-fusion molecules could be isolated and sequenced. Moreover, using the same viral libraries, a plaque-lift assay was established that allowed the identification of secreted, intracellular, and membrane proteins.

Animals↗
PubMed2001

NADH/NADPH oxidase p22 phox C242T polymorphism and lipid peroxidation in coronary artery disease.

The nicotinamide adenine dinucleotide (NADH)/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system is a major source of superoxide anion (.O2-) production in the human vasculature and may therefore influence lipid peroxidation and severity of atherosclerosis. This study aimed to investigate a hypothetical influence of the p22 phox C242T polymorphism on the generation of malondialdehyde (MDA), extent and clinical onset of coronary artery disease (CAD) in patients. We studied 108 male Caucasians with angiographically documented CAD and 45 controls free of vascular disease under 60 years of age. p22 phox C242T genotypes and MDA levels were determined. Additional information was obtained from each subject on classic risk factors and clinical events of CAD. Genotype distribution in CAD-patients and controls was thymine-thymine (TT): 13.8% (13.3%), cytosine-thymine (CT): 46.3% (53.3%) and cytosine-cytosine (CC): 39.8% (33.3%), respectively. No significant influence was seen of the p22 phox C242T polymorphism on corresponding mean MDA levels in both groups. Furthermore, age at onset of first time angina pectoris (AP) and myocardial infarction (MCI) was not significantly different between genotype groups. It is concluded that the C242T polymorphism of the p22 phox gene is not associated with lipid peroxidation as measured by MDA, and is not a genetic risk marker for CAD Caucasians.

Adult↗
PubMed2001

Hyperhomocyst(e)inaemia, but not MTHFR C677T mutation, as a risk factor for non-arteritic ischaemic optic neuropathy.

BACKGROUND/AIMS: Hyperhomocyst(e)inaemia has been identified as a strong risk factor for stroke, myocardial infarction, and deep vein thrombosis. A point mutation of methylene tetrahydrofolate reductase (MTHFR C677T) has been associated with increased plasma homocyst(e)ine levels. To investigate whether hyperhomocyst(e)inaemia and/or MTHFR C677T mutation are associated with non-arteritic ischaemic optic neuropathy (NAION), a case-control study including 59 consecutive patients with NAION and 59 controls matched for age and sex was performed. METHODS: Fasting plasma homocyst(e)ine levels, MTHFR C677T genotypes, and plasma levels of folate and vitamin B-12 were determined. RESULTS: Mean plasma homocyst(e)ine levels were significantly higher in patients than in controls (11.8 (SD 5.7) micromol/l v 9.8 (2.5) micromol/l, p = 0.02). The odds ratio for patients with homocyst(e)ine levels exceeding the 95th percentile of control homocyst(e)ine levels was 5.8 (95% CI 1.5-21.4). Mean plasma folate levels were significantly lower in patients than in controls (4.3 (1.7) ng/ml v 5.5 (1.9) ng/ml, p = 0.001), whereas plasma vitamin B-12 levels did not differ significantly. Prevalence of the MTHFR C677T mutation was not significantly increased in patients with NAION compared with controls. CONCLUSION: These results suggest that hyperhomocyst(e)inaemia, but not MTHFR C677T mutation is associated with NAION. Determination of plasma homocyst(e)ine levels might be of diagnostic value in patients with NAION.

Aged↗