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1.
Ir J Med Sci ; 173(4): 200-3, 2004.
Article in English | MEDLINE | ID: mdl-16323614

ABSTRACT

BACKGROUND: Recent data suggest that inflammatory reactions are involved in the pathogenesis of cerebral ischaemia. AIM: To investigate whether certain inflammatory genetic polymorphisms are associated with the occurrence of ischaemic stroke. METHODS: We investigated the prevalence of six polymorphisms in cytokine genes (IL-6, TNF-alpha, TNF-beta, IL-1beta, IL-10, and IL-1Ralpha) in a group of ischaemic stroke patients (n = 105) and in a control population (n = 389). We analysed the prevalence of these polymorphisms in different stroke subtypes and in relation to outcome six months post-stroke. RESULTS: There was no significant variation in cytokine gene polymorphism frequencies between control and stroke populations or for different stroke subtypes. Subgroup analysis demonstrated that the prevalence of the IL-6 -174 CC genotype was significantly lower in stroke patients without a history of hypertension compared to controls. CONCLUSION: The IL6 -174 CC genotype may be protective against stroke in those patients who have no history of hypertension. Further studies are required to verify these findings.


Subject(s)
Brain Ischemia/genetics , Interleukin-6/genetics , Polymorphism, Genetic , Adolescent , Adult , Aged , Alleles , Chi-Square Distribution , Female , Gene Frequency , Genotype , Humans , Hypertension , Interleukin-1/genetics , Interleukin-10/genetics , Male , Middle Aged , Polymerase Chain Reaction , Prospective Studies , Tumor Necrosis Factor-alpha/genetics
2.
Genes Immun ; 4(8): 533-40, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14647192

ABSTRACT

Patients with meningococcal disease have increased plasma levels of proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha, with higher levels associated with fatal outcome. This study investigated whether polymorphisms in genes encoding these cytokines, and in those encoding anti-inflammatory IL-10 and IL-1Ra, are associated with the outcome in patients with meningococcal disease. Seven polymorphisms were genotyped in 183 meningococcal disease patients and 389 controls. The IL-6 -174 G/G and IL-10 -1082 A/A genotypes were more frequent in nonsurvivors compared with survivors (P=0.023 IL-6, 0.25 IL-10), and in patients with severe disease compared to those with mild disease (P=0.037 IL-6, 0.0078 IL-10). An association was also found between meningococcal disease and the IL-1RN VNTR polymorphism, but no association was observed with the LTA +252, TNF -308, IL-10 -592, or IL-1B +3953 polymorphisms. We conclude that genetic variability in the IL-6, IL-10, and IL-1RN genes is associated with a poor outcome in meningococcal disease.


Subject(s)
Bacteremia/genetics , Cytokines/genetics , Meningococcal Infections/genetics , Phenotype , Polymorphism, Genetic , Adult , Cytokines/blood , DNA Primers , Female , Gene Frequency , Genotype , Humans , Interleukin 1 Receptor Antagonist Protein , Interleukin-1/genetics , Interleukin-10/genetics , Interleukin-6/genetics , Ireland , Male , Middle Aged , Minisatellite Repeats/genetics , Polymorphism, Restriction Fragment Length , Predictive Value of Tests , Sialoglycoproteins/genetics , Tumor Necrosis Factor-alpha/genetics
3.
Ir J Med Sci ; 171(1): 37-9, 2002.
Article in English | MEDLINE | ID: mdl-11993593

ABSTRACT

BACKGROUND: The genetic variation which underlies the thermolability and low enzyme activity of 5,10-methylenetetrahydrofolate reductase (MTHFR; C677T) has been extensively studied in many populations, including the Irish population. AIM: To describe the examination of the C677T substitution in two new control samples drawn from the Irish population. METHODS: A collection of 487 serum samples was obtained through the blood transfusion services of both the Republic of Ireland and Northern Ireland and a further 115 samples from volunteers. RESULTS: In both samples, the frequency of the thermolabile/low enzyme activity allele (T) was higher than that previously reported for the Irish population. CONCLUSION: This finding thus supports the need for a greater use of internal control/family-based association studies, as opposed to the classic case control study design, when assessing the contribution of the MTHFR T allele to disease processes.


Subject(s)
Oxidoreductases Acting on CH-NH Group Donors/genetics , Adult , Alleles , Female , Gene Frequency , Genetic Variation , Humans , Ireland/epidemiology , Male , Methylenetetrahydrofolate Reductase (NADPH2) , Northern Ireland/epidemiology
4.
Am J Med Genet ; 105(5): 422-5, 2001 Jul 08.
Article in English | MEDLINE | ID: mdl-11449393

ABSTRACT

Recent evidence that 5HT-2A may be subjected to genomic imprinting prompted us to examine a collection of Irish family trios (an affected individual and both parents) for evidence of an association between 5HT-2A and bipolar disorder. Family trios offer an advantage over case control studies in regard to genomic imprinting since with family trios it is possible to trace the path of alleles from the parents to the offspring. Using haplotype-based haplotype relative risk (HHRR) and transmission/disequilibrium (TDT) analyses, no evidence was found for an association of 5HT-2A with bipolar affective disorder under the assumption of no imprinting and of imprinting.


Subject(s)
Bipolar Disorder/genetics , Genomic Imprinting , Receptors, Serotonin/genetics , Alleles , DNA/genetics , Family Health , Female , Gene Frequency , Genotype , Haplotypes , Humans , Male , Receptor, Serotonin, 5-HT2A
5.
Am J Med Genet ; 105(2): 152-8, 2001 Mar 08.
Article in English | MEDLINE | ID: mdl-11304828

ABSTRACT

Following the description of linkage of markers at chromosome 4p16 to bipolar disorder in several families [Blackwood et al., 1996], and the association of the alleles of a polymorphism closely linked to D5 dopamine receptor gene with schizophrenia [Williams et al., 1997], we have looked for linkage disequilibrium between a series of microsatellite markers from this region and major psychoses including schizophrenia, bipolar disorder, and unipolar major depressive disorder. A significant increase in the frequency of the 148 bp allele of DRD5 (P = 0.024) and the 244 bp allele of D4S615 (P = 0.001) was found in patients with schizophrenia (n = 158 DRD5; n = 133 D4S615), compared with patients with bipolar disorder (n = 270 DRD5; n = 107 D4S615), or controls without psychiatric illness (n = 437 DRD5; n = 309 D4S615). The frequency of the 148 bp allele of DRD5 was also increased in schizophrenia over unipolar major depressive disorder (n = 65). D4S615 was not typed in unipolar disorder. The estimated odds ratios confirmed that the 148 bp allele of DRD5 and the 244 bp allele of D4S615 conferred increased risk of schizophrenia. Estimated Haplotype (EH) analysis of 174 controls and 128 patients with schizophrenia who were typed for both markers confirmed the strong associations with these alleles but did not show evidence that the markers were in linkage disequilibrium with each other even though they lie approximately 150 kb apart. The data are consistent with an association between markers close to the D5 dopamine receptor and schizophrenia, but not bipolar disorder or unipolar major depression.


Subject(s)
Bipolar Disorder/genetics , Microsatellite Repeats , Receptors, Dopamine D1/genetics , Schizophrenia/genetics , Alleles , Case-Control Studies , Chromosomes, Human, Pair 4 , Family Health , Female , Gene Frequency , Genetic Linkage , Genotype , Haplotypes , Humans , Linkage Disequilibrium , Male , Odds Ratio , Parents , Polymorphism, Genetic , Receptors, Dopamine D5
6.
Br J Ophthalmol ; 85(1): 88-90, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11133719

ABSTRACT

BACKGROUND: Raised levels of total plasma homocysteine (tHcy) are associated with an increased risk of retinal vascular occlusive disease. A thermolabile form of a pivotal enzyme in homocysteine metabolism, methylenetetrahydrofolate reductase (MTHFR), has been associated with vascular occlusive disease and raised tHcy levels. The relation between thermolabile MTHFR genotype, tHcy, and retinal vascular occlusive disease has not been determined. METHODS: A retrospective case-control study involving hospital based controls and cases with retinal vascular occlusions in whom tHcy levels had been determined was undertaken. Genotyping for the MTHFR 677 C-T mutation that specifies the thermolabile form of the enzyme was performed by established methods in all subjects. The relation between homozygosity for thermolabile MTHFR genotype (TT), raised tHcy levels, and risk of retinal vascular occlusive disease was examined. RESULTS: 87 cases of retinal vascular occlusive disease (mean age 68.7 years) comprising 26 cases of retinal artery occlusion and 61 of retinal vein occlusion were compared with 87 controls (mean age 70.2 years). The TT genotype did not confer a significantly increased risk of retinal vascular occlusive disease. The mean tHcy level was significantly higher in the cases than in the controls (p<0.0001). Overall, and in both the cases and controls, the frequency of the TT genotype was higher in those with normal tHcy levels than in those with increased levels of tHcy. However, the TT genotype did not significantly alter the risk of increased tHcy levels in these patients. CONCLUSIONS: The TT genotype is not associated with an increased risk of retinal vascular occlusive disease or increased tHcy levels in this group of elderly patients. In older patients, nutritional rather than genetic factors may be more important in increasing tHcy levels, a known risk factor for retinal vascular occlusive disease.


Subject(s)
Homocysteine/blood , Oxidoreductases Acting on CH-NH Group Donors/genetics , Retinal Artery Occlusion/genetics , Retinal Vein Occlusion/genetics , Aged , Case-Control Studies , Female , Genotype , Hot Temperature , Humans , Male , Methylenetetrahydrofolate Reductase (NADPH2) , Middle Aged , Point Mutation , Retinal Artery Occlusion/blood , Retinal Vein Occlusion/blood , Retrospective Studies , Risk Factors
7.
Psychiatr Genet ; 11(4): 223-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11807414

ABSTRACT

Oestrogen, a sex steroid hormone, has long been hypothesized to be involved in alterations to pathways involved in neurotransmission, and therefore may be involved in neuropsychiatric conditions including bipolar disorder. Indeed, certain depressive disorders in women have been found to be associated with low levels of oestrogen and can be much improved by the administration of this hormone. As the effects of oestrogen are most probably mediated through the oestrogen receptors (ER alpha and ER beta), the genes encoding these receptors may be possible candidates for association studies with bipolar disorder and other neuropsychiatric disorders. A number of studies, including previous results from this group, have reported modest evidence of linkage between both bipolar disorder and schizophrenia and a region of chromosome 14 (q22-q24), where the ER beta gene has been localized. In the present study, a sample of 102 Irish parent-proband trios were genotyped for a single nucleotide polymorphism within the ER beta gene (3' untranslated region, A1730G). However, the transmission/disequilibrium test failed to reveal evidence of a distortion in allele transmission to bipolar I (BPI) probands.


Subject(s)
Bipolar Disorder/genetics , Receptors, Estrogen/genetics , Chi-Square Distribution , DNA Primers , Depressive Disorder/genetics , Estrogen Receptor beta , Female , Heterozygote , Humans , Male , Polymerase Chain Reaction , Polymorphism, Single Nucleotide
8.
Am J Med Genet ; 96(6): 728-32, 2000 Dec 04.
Article in English | MEDLINE | ID: mdl-11121170

ABSTRACT

Conducting genome wide screens for evidence of genetic linkage has become a well-established method for identifying regions of the human genome harboring susceptibility loci for complex disorders. For bipolar disorder, a number of such studies have been performed, and several regions of the genome have potentially been implicated in the disorder. The classic design for a genome screen involves examining polymorphic genetic markers spaced at regular intervals throughout the genome, typically every 10 cM, for evidence of linkage. An alternative design, based on the observation that genes do not appear to be evenly distributed, was proposed, enabling the number of markers examined in a genome wide screen to be reduced. This article describes the application of such a modified screen to a collection of 48 Irish families with bipolar disorder, comprising a total of 82 affected sib-pairs. From the results obtained a number of regions are highlighted for further study. One of these regions (17q11.1-q12) coincides with the location of a candidate gene, the serotonin transporter, whereas others concur with the findings of published studies. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:728-732, 2000.


Subject(s)
Bipolar Disorder/genetics , Genetic Predisposition to Disease/genetics , Chromosome Mapping , DNA/genetics , Family Health , Female , Genome, Human , Humans , Lod Score , Male , Microsatellite Repeats
9.
Am J Med Genet ; 96(6): 845-9, 2000 Dec 04.
Article in English | MEDLINE | ID: mdl-11121194

ABSTRACT

Previously we obtained modest linkage evidence implicating 17q11. 1-12 in bipolar disorder. A modified genome screen, based on gene-rich regions, on a collection of Irish sib-pair nuclear families revealed excess allele sharing at markers flanking the gene encoding the serotonin transporter (5-HTT; hSERT). Here we describe a study designed to combine the advantages of family-based association studies with the consideration of multiple polymorphic markers within a candidate gene. Ninety-two Irish families, with a total of 106 proband-parent trios, have been genotyped for 3 previously known polymorphisms within hSERT (5-HTTLPR, intron 2 VNTR, and 3' UTR G/T). Data from two and three polymorphic marker haplotypes revealed a number of marker combinations that showed evidence supportive of association; the most significant being for polymorphisms 5-HTTLPR and 3' UTR G/T (global chi(2), 12.91, df 3, P = 0.005). In addition, modest evidence of association also was observed for 5-HTTLPR alone. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:845-849, 2000.


Subject(s)
Bipolar Disorder/genetics , Carrier Proteins/genetics , Haplotypes , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Nerve Tissue Proteins , Alleles , DNA/genetics , Family Health , Female , Gene Frequency , Genetic Markers , Genotype , Humans , Male , Serotonin Plasma Membrane Transport Proteins
10.
Br J Haematol ; 111(2): 559-61, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11122102

ABSTRACT

The prevalence of factor V (FV) Leiden among normal populations has primarily been determined using blood donors. This control group is carefully selected and therefore may not accurately reflect the true prevalence within the population. We assessed the prevalence of FV Leiden within the Irish population using Guthrie card samples randomly selected from all newborns. We compared this result with the prevalence of FV Leiden within blood donors. A novel nested polymerase chain reaction (PCR) method for FV Leiden was developed for analysis of the Guthrie card samples. There was no significant difference between the allele frequency within the Guthrie card samples and blood donors (2.07% vs. 2.35%, P = 0.66)


Subject(s)
Factor V , Infant, Newborn/blood , Adult , Aged , Blood Donors , Female , Gene Frequency , Heterozygote , Homozygote , Humans , Ireland , Male , Middle Aged , Polymerase Chain Reaction/methods , Prevalence
11.
Blood Coagul Fibrinolysis ; 11(7): 669-72, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11085288

ABSTRACT

The prothrombin G20210A polymorphism is associated with a threefold-increased risk of venous thrombosis. There is considerable variation in the reported prevalence of this polymorphism within normal populations, ranging from 0 to 6.5%. The prevalence within the Irish population has not been determined. A restriction fragment length polymorphism (RFLP)-based assay is commonly used for the detection of the prothrombin 20210A allele. This assay does not include a control restriction digest fragment and, consequently, failure of the enzyme activity or lack of addition of enzyme to the sample cannot be distinguished from wild-type prothrombin. We developed a RFLP-based assay, which incorporates an invariant digest site, resulting in the generation of a control digest fragment. Furthermore, we developed a nested polymerase chain reaction (PCR) method for the amplification and digestion of poor-quality or low-concentration DNA. In the Irish population studied, five of 385 (1.29%) were heterozygous and one patient was homozygous for the prothrombin 20210A polymorphism. This is the first reported data on an Irish or Celtic population and suggests that the allele frequency is similar to Anglo-Saxon populations. The nested PCR method successfully amplified and digested 100/100 (100%) of the archived samples; none of these samples could be analyzed by the standard single-round PCR method. In conclusion, nested PCR should be considered in the analysis of archived samples. Single-round PCR is appropriate for recently collected samples; however, an invariant control digest site should be incorporated in RFLP-based assays to validate the integrity of the digestion enzyme and limit the risk of false-negative results.


Subject(s)
Prothrombin/genetics , Base Sequence , DNA Primers/standards , Gene Frequency , Genetic Testing/methods , Genetic Testing/standards , Genotype , Humans , Ireland/epidemiology , Molecular Sequence Data , Point Mutation , Polymerase Chain Reaction/methods , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Prevalence , Reference Standards , Thrombophilia/epidemiology , Thrombophilia/genetics
13.
Am J Med Genet ; 92(3): 206-11, 2000 May 29.
Article in English | MEDLINE | ID: mdl-10817656

ABSTRACT

The human T developmental gene has been implicated in the etiology of neural tube defects (NTDs) on the basis both of mouse studies of its homologue, T (Brachyury), and of allelic association in a Caucasian population. We have investigated the frequency of the T allelic variant TIVS7-2 in 218 Irish NTD case-parent triads. This population showed the same trend as previously reported, with an excess of the TIVS7-2 allele among cases. Log-linear modeling of case and maternal genotypic effects within families indicated that TIVS7-2 was elevated in cases (relative risk, RR = 1.36) but not in mothers (RR = 0.91). The TIVS7-2 allele is markedly associated with cases born before 1980 (RR = 2.09; CI = 1.23-3.55; corrected p = 0.030), but not with more recent cases (RR = 0.92). Cases carrying a TIVS7-2 allele did not show any increased tendency to be homozygous for the thermolabile variant of the folate-dependent enzyme 5,10-methylene tetrahydrofolate reductase, which is an established genetic risk factor for NTDs. Since the incidence of NTDs has declined markedly in Ireland over the last few decades, we suggest that the T-associated risk is potentiated by nutritional or environmental risk factor(s), the impact of which have been diminishing over time.


Subject(s)
Fetal Proteins , Genetic Predisposition to Disease , Neural Tube Defects/genetics , Oxidoreductases Acting on CH-NH Group Donors/genetics , T-Box Domain Proteins/genetics , Adolescent , Adult , Alleles , Animals , DNA Mutational Analysis , Female , Genotype , Humans , Linkage Disequilibrium , Male , Methylenetetrahydrofolate Reductase (NADPH2) , Mice , Risk
14.
Psychiatr Genet ; 9(3): 129-34, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10551542

ABSTRACT

The phenomenon of anticipation has been demonstrated in several neuropsychiatric disorders and suggested for schizophrenia and bipolar affective disorder. Many conditions exhibiting anticipation have been shown to be caused by trinucleotide repeat (CAG/CTG) expansions. Some evidence suggests that these expansions also exist in individuals with schizophrenia and bipolar affective disorder. In this investigation, we analysed a polymorphic CAG repeat in the interleukin receptor gene (IL9R), mapped to the pseudoautosomal region Xq28 and Yq21 (a candidate region for schizophrenia and affective disorder). Two common alleles, differing by one repeat unit and two rare alleles were found in cases and controls. Allele frequencies of this repeat were investigated in Irish schizophrenic, bipolar disorder and ethnically matched control samples. We found no evidence of an increased frequency of larger CAG repeats in either the schizophrenic or bipolar affective disorder samples as a whole when compared to the controls. However, dividing the samples by sex demonstrated a significant association between bipolar affective disorder males and the larger allele (allele 2) (patients 54.8% vs controls 40.1%, chi2 = 6.7, P = 0.009). In addition, a decreased frequency of this allele has been observed in the female patients, but did not attain statistical significance (patients 37% vs controls 46%, chi2 = 2.1, P = 0.14). This provides preliminary evidence that this locus or a closely mapped DNA variant (in linkage disequilibrium with the CAG repeat) may be involved in the genetic susceptibility to bipolar affective disorder in males.


Subject(s)
Bipolar Disorder/genetics , Pseudogenes , Receptors, Interleukin/genetics , Schizophrenia/genetics , Trinucleotide Repeats , X Chromosome , Y Chromosome , Chromosome Mapping , DNA Primers , Family , Female , Humans , Male , Polymorphism, Genetic , Receptors, Interleukin-9 , Reference Values , Sex Characteristics
15.
Mol Psychiatry ; 4(5): 488-91, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10523823

ABSTRACT

Anticipation has attracted much interest and has been demonstrated in several neuropsychiatric disorders. For some disorders, this phenomenon has been found to correlate with the repeat number in large and unstable repeats (CAG/CTG). In addition, case control studies have suggested an increase in triplet repeat size in the psychoses. Recently, it was reported that the larger alleles (longer than 19 repeats) of the second potassium channel gene hSKCa3 are associated with schizophrenia in European and American samples. A similar trend, though not statistically significant, was also seen in bipolar disorder samples. This was further supported by an independent UK study.1 In this investigation, we have examined Irish familial schizophrenic patients, bipolar affective disorder patients and ethnically matched controls in an effort to replicate these findings. No significant differences between the patients and the control groups were observed. In addition, linkage analyses in the multiplex schizophrenic families showed no evidence for linkage or linkage disequilibrium. We concluded that the polymorphism of the second CAG repeat of the hSKCa3 gene is not a risk factor in schizophrenia or bipolar disorder, at least in the Irish population.


Subject(s)
Bipolar Disorder/genetics , Neuropeptides/genetics , Potassium Channels/genetics , Schizophrenia/genetics , Trinucleotide Repeats , Cohort Studies , Family Health , Female , Genetic Linkage , Genotype , Humans , Ireland , Male , Phenotype , Polymorphism, Genetic , Small-Conductance Calcium-Activated Potassium Channels
16.
Psychiatry Res ; 81(2): 125-31, 1998 Nov 16.
Article in English | MEDLINE | ID: mdl-9858030

ABSTRACT

In order to measure the intrafamilial correlation for age at onset and to examine gender resemblance among bipolar siblings, we assessed a sample of 130 bipolar patients belonging to 59 multiple affected sibships. To study the intrafamilial resemblance for age at onset and gender, we used the intraclass correlation and the sibship method, respectively. Within the whole sample, age at onset for affected siblings was correlated (rho = 0.42, P = 0.0001). Gender was randomly distributed among bipolar sibships, demonstrating the absence of gender resemblance among affected siblings. The existence of an intrafamilial correlation for age at onset among bipolar siblings suggests that this variable may assist in the identification of more heritable forms of the illness. No intrafamilial correlation was found for the gender of affected siblings, suggesting that familial vulnerability factors are not gender-specific.


Subject(s)
Bipolar Disorder/genetics , Genetic Predisposition to Disease/genetics , Adolescent , Adult , Age Factors , Bipolar Disorder/diagnosis , Female , Humans , Male , Middle Aged , Models, Genetic , Phenotype , Psychiatric Status Rating Scales , Sex Factors
17.
Psychiatr Genet ; 8(4): 221-5, 1998.
Article in English | MEDLINE | ID: mdl-9861640

ABSTRACT

Catechol-O-methyltransferase (COMT) catalyses the methylation, and hence the inactivation, of catecholamines including the neurotransmitters dopamine and noradrenaline. There is evidence implicating COMT as a candidate gene for a number of neuropsychiatric conditions including bipolar disorder. A long recognized population variation in COMT activity exists and it has recently been established that variation in enzyme activity results from a polymorphic genetic variation within the COMT gene which can be readily assayed as a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). A collection of 60 Irish bipolar I probands have been genotyped together with their parents. Tests comparing transmitted and non-transmitted alleles provide no evidence that the polymorphism contributes to a susceptibility to bipolar disorder within the sample as a whole. However, amongst female bipolar I probands (n = 30) there was a tendency for the low-activity allele of COMT to be preferentially transmitted. Furthermore, a re-examination of an Irish case-control sample resulted in a similar observation amongst female bipolar I sufferers and pooling the data sets strengthened the findings.


Subject(s)
Bipolar Disorder/genetics , Catechol O-Methyltransferase/genetics , Chromosomes, Human, Pair 22/genetics , Alleles , Bipolar Disorder/enzymology , Bipolar Disorder/epidemiology , Case-Control Studies , Catechol O-Methyltransferase/analysis , Female , Genetic Predisposition to Disease , Genotype , Haplotypes/genetics , Humans , Ireland/epidemiology , Male , Parents , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Risk
18.
Biol Psychiatry ; 44(1): 47-51, 1998 Jul 01.
Article in English | MEDLINE | ID: mdl-9646882

ABSTRACT

BACKGROUND: Disturbances in central nervous system Na+, K+ adenosine triphosphatase (ATPase) activity have previously been proposed as being involved in the pathophysiology of bipolar mood disorder. METHODS: We have examined one particular alpha subunit of this enzyme for allelic association in a sample of 85 Irish bipolar patients and 85 matched controls. RESULTS: There was evidence for an overall allelic association between the disease and a dinucleotide polymorphism within the ATP1A3 gene (p = .022). Subjects were then analyzed on the basis of a number of criteria, and the significance of the association increased when cases were divided based on the nature of the first episode. Patients who presented with a depressive episode first showed a significant association (p = .001) with this polymorphism. CONCLUSIONS: The results presented here provide preliminary evidence of an association between bipolar disorder and an alpha subunit of Na+, K+ ATPase, the expression of which predominates in the brain.


Subject(s)
Bipolar Disorder/genetics , Sodium-Potassium-Exchanging ATPase/genetics , Adult , Aged , Alleles , Bipolar Disorder/epidemiology , Bipolar Disorder/physiopathology , Brain/metabolism , Case-Control Studies , Chi-Square Distribution , Dinucleotide Repeats/genetics , Female , Gene Expression , Genetic Markers , Humans , Ireland/epidemiology , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic , Sodium-Potassium-Exchanging ATPase/biosynthesis , Sodium-Potassium-Exchanging ATPase/physiology
19.
Biol Psychiatry ; 42(10): 876-81, 1997 Nov 15.
Article in English | MEDLINE | ID: mdl-9359972

ABSTRACT

The hypothesis that expanded trinucleotide repeats (TNRs) contribute to the pathogenesis of bipolar disorder has received strong support from recent studies showing that, on average, bipolar patients carry larger repeat sequences of the TNR motif CAG/CTG than do controls. It has been postulated that intergenerational expansion of a TNR may be responsible for the tendency for age of onset to become earlier in younger generations (anticipation) observed in some bipolar pedigrees, and that length polymorphism may account for variability in clinical phenotype. We have used the method of repeat expansion detection to examine these predictions in a sample of 133 Caucasian DSM-III-R bipolar I probands from the British Isles. We found no evidence to support the notion that CAG/CTG TNR genes are major determinants of phenotypic severity or age at onset in the population examined, and conclude that for most cases of bipolar disorder TNR genes may operate as susceptibility genes rather than as single genes of major effect.


Subject(s)
Bipolar Disorder/genetics , Phenotype , Trinucleotide Repeats/genetics , Adult , Bipolar Disorder/diagnosis , Bipolar Disorder/psychology , Female , Humans , Male , Middle Aged , Severity of Illness Index
20.
Biol Psychiatry ; 42(6): 486-94, 1997 Sep 15.
Article in English | MEDLINE | ID: mdl-9285084

ABSTRACT

Seven families, multiply affected by bipolar mood disorder, have been collected from the Irish population and have been genotyped with microsatellite markers from the pericentromeric region of chromosome 18, a region that has been implicated as a site for a susceptibility gene for this relative common psychiatric disorder. The families significantly excluded linkage of bipolar disorder to this region under various models. Although the data provided no evidence of linkage heterogeneity among families, the number of families investigated may be too small to exclude completely the possibility of linkage in a small number of families.


Subject(s)
Bipolar Disorder/genetics , Chromosomes, Human, Pair 18/physiology , Adult , Bipolar Disorder/psychology , Female , Genetic Linkage , Genotype , Humans , Ireland , Male , Microsatellite Repeats , Models, Genetic , Pedigree
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