Associations of oxytocin receptor gene (
OXTR) variants and autism spectrum disorders (ASD) have been reported in earlier studies; in one of the studies associations with IQ and daily living skills ...were found additionally. Variations of the oxytocin receptor gene might also regulate affect, attachment and separation beyond the diagnostic borders of autism. We tested hypotheses of associations between positive and negative affects and social and emotional loneliness (285 adults), IQ (117 adolescents) and polymorphisms of the oxytocin receptor gene (
OXTR rs53576, rs2254298 and rs2228485) in normal subjects. Individuals with the oxytocin
OXTR rs53576 A/A genotype showed lower positive affect scores (
F
=
5.532, df
=
1;
p
=
0.019). This effect was restricted to males (
F
=
13.098, df
=
1;
p
=
0.00047). Haplotypes constructed with the three markers were associated with positive affect (
p
=
0.0012), negative affect (
p
<
0.0001) and emotional loneliness (
p
<
0.0001). Non-verbal intelligence was significantly reduced in rs53576 A/A adolescents (
T
=
2.247,
p
=
0.027). Our findings support a role for the oxytocin receptor haplotypes in the generation of affectivity, emotional loneliness and IQ.
Summary
To investigate the relationship between clinical phenotype, clotting activity (FVIIc) and FVII genotype, a multi-center study of factor VII (FVII) congenital deficiency with centralized ...genotyping and specific functional assays was carried out. FVII mutations characterized in patients (n=313) were extremely heterogeneous (103 different, 22 novel). Clinical phenotypes ranged from asymptomatic condition, including 15 homozygotes and 14 double heterozygotes, to patients with a severe disease char-acterized by life-threatening and disabling symptoms (CNS, GI bleeding and hemarthrosis) strongly associated with an early age of presentation. Based on type and number of symptoms we classified 90 'severe' (median FVIIc 1.4%, IQR Interquartile Range 0.9–3.8), 83 'moderate' (FVIIc 3%, IQR 1–21.7), and 140 'mild' bleeders (FVIIc 14%, IQR 3–31). The significantly different FVIIc levels, and the decreasing prevalence of homozygotes or double heterozygotes among severe (98%), moderate (84%) and mild (56%) bleeders, further support our classification. The excess of females among moderate bleeders (female/male ratio =2.6) is attributable to menorrhagia. There was no evidence for modulation of clinical features by frequent functional polymorphisms. Homozygotes for the same mutation (Ala294Val; 11125del C) with similar FVIIc and FXa generation levels, showed striking differences in clinical phenotypes. Our study depicts the ample clinical picture of this rare disorder, proposes a severity classification and provides arguments for the early management of the disease in the severe cases. Genotype-phenotype relationships indicate the presence of major environmental and/or extragenic components modulating expressivity of FVII deficiency.
Abstract
Background/aims: The application of intranasal oxytocin enhances facial emotion recognition in normal subjects and in subjects with autism spectrum disorders (ASD). In addition, various ...features of social cognition have been associated with variants of the oxytocin receptor gene (OXTR). Therefore, we tested for associations between mind-reading, a measure for social recognition and OXTR polymorphisms. Methods: 76 healthy adolescents and young adults were tested for associations between OXTR rs53576, rs2254298, rs2228485 and mind-reading using the "Reading the Mind in the Eyes Test" (RMET). Results: After Bonferroni correction for multiple comparisons, rs2228485 was associated with the number of incorrect answers when subjects evaluated male faces (P =0.000639). There were also associations between OXTR rs53576, rs2254298 and rs2228485 and other RMET dimensions according to P <0.05 (uncorrected). Conclusion: This study adds further evidence to the hypothesis that genetic variations in the OXTR modulate mind-reading and social behaviour.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Hyperhomocysteinemia is associated with atherosclerotic risk. Although vitamins can lower homocysteine (Hcy), information about effects on atherosclerosis is scarce.
We used carotid intima-media ...thickness (IMT) as an accepted marker of atherosclerotic changes. Fifty patients (60
±
8 years) with IMT
≥
1
mm were included. In a double blind, randomized trial they received daily 2.5
mg folic acid, 25
mg Vitamin B6, and 0.5
mg Vitamin B12 or placebo for 1 year.
In the treatment group, Hcy decreased from 10.50
±
3.93 to 6.56
±
1.53
μmol/l (
P
<
0.0001), whereas it remained unchanged in the placebo group (10.76
±
2.36 versus 10.45
±
3.30
μmol/l). IMT decreased from 1.50
±
0.44 to 1.42
±
0.48
mm (
P
=
0.034) in the treatment group, whereas it increased from 1.47
±
0.57 to 1.54
±
0.71
mm in the placebo group. The mean individual changes of IMT between both groups differed significantly (−0.08
±
0.17 versus 0.07
±
0.25
mm,
P
=
0.019). Multiple regression analysis revealed that the observed effect on IMT depended only on medication.
Vitamin supplementation significantly reduces IMT in patients at risk. This effect is independent of Hcy concentration.
Summary
Two families with 'factor X(FX)-Riyadh' have been identified (one of them related to the originally reported family). Affected members of both families exhibit prolongation in prothrombin ...time (PT) with normal partial thromboplastin time (PTT) and low assay levels of FX, when measured by PT-based assay. They do not have clinical bleeding diathesis, regardless of the PT prolongation. FX genes of the affected family members were analyzed by sequence analysis. A novel missense mutation in exon 4 of the FX gene, which causes the Glu51Lys substitution in the first epidermal growth factor-like domain of FX was found. The Glu51Lys mutation represents a type II mutation with low FX coagulant activity in the extrinsic pathway and normal FX antigen levels. This mutation may result in disruption of the predicted H-bonding between residue Glu51 of FX and the Asn199 residue of the tissue factor (TF) in the FX/TF/factorVIIa ternary complex, producing the phenotype 'FX deficiency Riyadh', with prolonged PT and normal PTT.
Both reduced postsynaptic dopamine D(2) receptor function and the character variable self-directedness (SDD) are related to the level of alcohol consumption. We examined for interactions between DRD2 ...exon 8(rs6276), a polymorphism which has been associated with various alcohol-related phenotypes, SDD and alcohol consumption.
A total of 144 male and 186 female probands with alcohol dependence or abuse diagnoses and without were included in the study. All subjects were assessed with the alcohol section of the Semi-Structured Assessment for the Genetics of Alcoholism and the Temperament and Character Inventory.
Male probands with A/A genotype reported significantly higher alcohol consumption in a typical week (ANOVA; p = 0.024); those with A/A genotype and low SDD showed particularly high consumption levels (interaction DRD2 x SDD: p = 0.019). Alcohol dependence/abuse (DSM-IV) but not nicotine dependence was also relevant for higher alcohol consumption (trend: p = 0.052). In the female group, only alcohol disorders predicted alcohol consumption.
Our findings support a role for a gene-personality interaction of DRD2 exon 8 x SDD in alcohol consumption in males.
Summary
An association between the factor V Leiden variant and an increased risk of pregnancy loss has been reported. Most previous studies were performed with clinically recruited patients and ...controls. This approach may cause selection bias. The present analysis was performed with the aim to investigate the association between the factor V Leiden mutation and the risk of stillbirth in a population-based sample.
The Study of Health in Pomerania (SHIP) is a survey that was carried out in North East Germany. A random sample from the population aged 20 to 79 years was taken. The total SHIP population comprised 4,310 participants. The presence of the factor V Leiden variant was determined by PCR and
Mnl
I digestion. The presence of the factor V Leiden variant was neither associated with the number of pregnancies nor with the number of children per women. Data from 1,768 females who had at least one pregnancy with known outcome was available for the present analysis. Seventy-three women (4.1%) reported at least one stillbirth. Women with and without the factor V Leiden mutation did not differ with respect to the number of women with at least one stillbirth (OR for factor V Leiden variant 1.57; 95%-CI 0.76 – 3.25). Furthermore, the number of women with two or more stillbirths, the number of stillbirths per affected woman and the number of stillbirths per number of pregnancies per woman was similar between both genotype groups.
In conclusion, there is no association between the factor V Leiden mutation and the risk of stillbirth in a representative population sample.
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