TY  - JOUR
AB  - Genetic variations affecting the course of depressive symptoms in patients with coronary artery disease (CAD) have not yet been well studied. Therefore, we set out to investigate whether distinct haplotypes of the two insertion/deletion polymorphisms in the serotonin-transporter-linked polymorphic region (5-HTTLPR) and the angiotensin I-converting enzyme (ACE) gene located on chromosome 17 can be identified as risk factors for trajectories of depression. Clinical and genotyping data were derived from 507 depressed CAD patients participating in the randomized, controlled, multicenter Stepwise Psychotherapy Intervention for Reducing Risk in Coronary Artery Disease (SPIRR-CAD) trial, of whom the majority had an acute cardiac event before study inclusion. Depression scores on the Hospital Anxiety and Depression Scale (HADS) were assessed at baseline and at five follow-up time points up to 2 years after study entrance. At baseline, depression scores did not significantly differ between patients carrying the risk haplotype ACE D/D, 5-HTTLPR I/I (n = 46) and the non-risk haplotypes (n = 461, 10.9 ± 2.7 versus 10.4 ± 2.5, p = 0.254). HADS-depression scores declined from study inclusion during the first year irrespective of the genotype. At each follow-up time point, HADS-depression scores were significantly higher in ACE D/D, 5-HTTLPR I/I carriers than in their counterparts. Two years after study inclusion, the mean HADS depression score remained 1.8 points higher in patients with the risk haplotype as compared to subjects not carrying this haplotype (9.9 ± 4.2 versus 8.1 ± 4.0, p = 0.009). In summary, the presence of the ACE D/D, 5-HTTLPR I/I haplotype may be a vulnerability factor for comorbid depressive symptoms in CAD patients.
AU  - Meyer, T.*
AU  - Rothe, I.*
AU  - Staab, J.*
AU  - Deter, H.C.*
AU  - Fangauf, S.V.*
AU  - Hamacher, S.*
AU  - Hellmich, M.*
AU  - Jünger, J.*
AU  - Ladwig, K.-H.
AU  - Michal, M.*
AU  - Petrowski, K.*
AU  - Ronel, J.*
AU  - Söllner, W.*
AU  - Weber, C.*
AU  - de Zwaan, M.*
AU  - Williams, R.B.*
AU  - Albus, C.*
AU  - Herrmann-Lingen, C.*
C1  - 59024
C2  - 48544
CY  - 233 Spring St, New York, Ny 10013 Usa
SP  - 631-648
TI  - Length polymorphisms in the angiotensin i-converting enzyme gene and the serotonin-transporter-linked polymorphic region constitute a risk haplotype for depression in patients with coronary artery disease.
JO  - Biochem. Genet.
VL  - 58
IS  - 4
PB  - Springer/plenum Publishers
PY  - 2020
SN  - 0006-2928
ER  - 

TY  - JOUR
AB  - Two lactate dehydrogenase (LDH) mutations were recovered independently among offspring of ethylnitrosourea-treated male mice by screening for alterations of isoelectric focusing pattern in liver homogenates. Investigations of physicochemical and kinetic properties of the mutant enzymes indicated that the mutant traits resulted from point mutations at the Ldh-1 structural locus. Therefore, the new alleles were designated Ldh-1a-m5Neu and Ldh-1a-m6Neu, respectively. Both mutant alleles code for proteins which exhibit an altered stability to heat, in addition to changes in isoelectric focusing pattern and a reduction in anodal electrophoretic mobility. While LDH-Aa-m5Neu proteins are markedly less heat stable, LDH-Aa-m6Neu proteins are more heat stable than the wild-type enzyme. Furthermore, a small elevation of Km for pyruvate, a slightly reduced inhibition by high pyruvate concentrations, and a slight acidic shift of the pH activity profile distinguish LDH-Aa-m6Neu from both wild-type and LDH-Aa-m5Neu enzymes. Significant alterations of LDH activity were detected in some tissues from LDH-Aa-m5Neu individuals but not in those from LDH-Aa-m6Neu animals. Erythrocytes and blood of LDH-Aa-m5Neu mutants revealed activity levels which were reduced by approximately 6 and 13% compared with those of wild types in heterozygous and homozygous individuals, respectively. In addition, an elevation of approximately 6% in LDH activity was found in skeletal muscle in homozygous mutants. Consistent with the unaltered or only slightly altered LDH activity in tissues, the genetic as well as the physiological characterization yielded no easily detectable effects from either mutation on metabolism or fitness of the affected individuals.
AU  - Merkle, S.
AU  - Pretsch, W.
C1  - 40647
C2  - 38013
SP  - 49-59
TI  - Characterization of two electrophoretic lactate dehydrogenase-A mutants in Mus musculus.
JO  - Biochem. Genet.
VL  - 30
IS  - 1-2
PY  - 1992
SN  - 0006-2928
ER  - 

TY  - JOUR
AB  - Two glucose-6-phosphate isomerase (GPI) mutants with approximately 60% residual activity in blood compared to wild type have been independently detected in offspring derived from 1-ethyl-1-nitrosourea-treated male mice. Homozygous mutants with about 20% residual activity were recovered in progeny of inter se matings of heterozygotes. However, in both mutant lines the number of homozygous mutants was less than expected suggesting an increased lethality of these animals. Results of linkage studies and of investigations of physicochemical properties of the mutant enzymes indicate point mutations at theGpi-1s structural locus on chromosome 7. Based on these findings the two new alleles were designatedGpi-1s b-m1Neu andGpi-1s b-m2Neu, respectively. The b-m1Neu allele codes for an erythrocyte enzyme which, in the homodimeric form, exhibits a decreased stability toward heat and urea, an altered isoelectric point, normalpH dependence, an increasedK m for fructose-6-phosphate, and increasedK i's for 6-phosphogluconate and 2,3-diphosphoglycerate (2,3-DPG) compared to the wild-type enzyme. The GPI-1sb-m2Neu homodimer, in contrast, is characterized by an even stronger instability, slightly alteredpH dependence, an increasedK i for 2,3-DPG, normal other kinetics, and normal isoelectric point. The different degree of stability of the mutant homodimersin vitro seems to be reflected in a different degree of stabilityin vivo, since GPI deficiency in general is more strongly expressed in the tissues of the homozygousGpi-1s b-m2Neu mutant compared to the homozygousGpi-1s b-m1Neu mutant. The similarity of the mutant enzymes to the allozymes found in human GPI deficiencies indicates the GPI deficient mouse mutants to be excellent models for the human disease.
AU  - Pretsch, W.
AU  - Merkle, S.
C1  - 18134
C2  - 10993
SP  - 97-110
TI  - Glucose Phosphate Isomerase Enzyme-Activity Mutants in Mus musculus: Genetical and Biochemical Characterization.
JO  - Biochem. Genet.
VL  - 28
IS  - 1
PY  - 1989
SN  - 0006-2928
ER  -