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1.
Int J Mol Sci ; 25(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39000519

RESUMO

The aim of the present study was to investigate the impact of CCR5 Δ32 and CTLA-4 polymorphisms on the response to IFN-ß treatment in our cohort of MS patients from Croatia and Slovenia. Genomic DNA was obtained from 295 MS patients (230 female; 65 male) classified as responders (n = 173) and non-responders (n = 122) based on clinical criteria for treatment efficacy. Genotyping was performed via PCR/PCR-RFLP. No significant differences in the genotype/allele frequencies of CCR5Δ32 and CTLA-4 +49 A/G were detected between male responders and non-responders. A significantly higher prevalence (p = 0.039) of the CTLA-4 +49 AA genotype was found in female responders (42.1%) compared to non-responders (28.9%). Using multiple forward regression analysis, the CTLA-4 +49 AA genotype significantly predicted a positive response to IFN-ß therapy in females (p = 0.011) and contributed to 4.5% of response variability. Furthermore, the combined presence of the CCR5Δ32 wtwt/CTLA-4 +49 AA genotype significantly predicted a positive response to treatment in females (p = 0.025). The age at disease onset, pretreatment relapse rate, and baseline EDSS score were not reliable predictors of treatment response in MS patients. Our results indicate that the presence of the CCR5Δ32 polymorphism was not associated with the response to IFN-ß treatment, whereas the CTLA-4 +49 polymorphism showed a positive correlation with an optimal response in female patients.


Assuntos
Antígeno CTLA-4 , Frequência do Gene , Interferon beta , Esclerose Múltipla , Polimorfismo de Nucleotídeo Único , Receptores CCR5 , Humanos , Feminino , Masculino , Antígeno CTLA-4/genética , Receptores CCR5/genética , Interferon beta/uso terapêutico , Eslovênia , Adulto , Croácia , Esclerose Múltipla/genética , Esclerose Múltipla/tratamento farmacológico , Pessoa de Meia-Idade , Genótipo , Resultado do Tratamento
2.
Pharmacogenet Genomics ; 27(6): 232-235, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28430710

RESUMO

We investigated the effect of the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene on the response to interferon-ß (IFN-ß) therapy in Croatian and Slovenian patients with multiple sclerosis (MS). A total of 275 IFN-ß treated MS patients [162 responders (Rs) and 113 nonresponders (NRs)] were genotyped by PCR. The ACE I/D genotype distribution and allele frequencies did not differ between female Rs and NRs. However, male NRs tended to have a greater prevalence of the DD genotype (P=0.073; odds ratio: 2.64; 95% confidence interval: 0.91-7.60) and a significantly higher frequency of the D allele (P=0.022; odds ratio: 2.43; 95% confidence interval: 1.13-5.20) than male Rs. Multiple forward stepwise regression analysis indicated that the negative response to IFN-ß therapy was associated with the ACE-DD genotype in men (ß=0.371; multiple R change: 0.132; P=0.009) and a higher pretreatment relapse rate in both men (ß=-0.438; multiple R change: 0.135; P=0.015) and women (ß=-0.208; multiple R change: 0.042; P=0.034). The ACE I/D polymorphism and pretreatment relapse rate accounted for ∼26.7% of the IFN-ß response variability among the men in the sample. Further studies of a larger number of MS patients from different populations are necessary to evaluate these preliminary findings.


Assuntos
Antineoplásicos/uso terapêutico , Mutação INDEL , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Peptidil Dipeptidase A/genética , Adulto , Croácia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Esclerose Múltipla/genética , Variantes Farmacogenômicos , Eslovênia , Resultado do Tratamento , Adulto Jovem
3.
J Neural Transm (Vienna) ; 124(4): 511-518, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28028641

RESUMO

We investigated the relationship between the functional insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and the risk of nicotine dependence in Croatian schizophrenia patients. We also tested whether interactions between ACE-I/D polymorphism and smoking status affected the clinical psychopathology findings in patients as measured using Positive and Negative Symptom Scale (PANSS) scores. Polymerase chain reaction analysis was used to genotype 267 chronically ill schizophrenia patients (140 males/127 females). There were no significant differences in the distribution of ACE genotypes and alleles in male or female schizophrenia patients who were stratified based on their smoking status. However, there was a trend toward a difference in the ACE genotype distribution in female smokers vs. nonsmokers (χ 2 = 5.13, p = 0.077) that was due mainly to the significant overrepresentation of ACE-ID heterozygous genotypes in female smokers compared to nonsmokers (62.3 vs. 42.0%, p = 0.025). ACE-ID heterozygous females had about a twofold higher smoking risk than ACE-II and ACE-DD homozygous carriers (OR = 2.29, 95% CI 1.1-4.7, p = 0.026). We observed no contribution of the ACE genotype-smoking interaction to PANSS psychopathology. This is the first study to investigate the possible association between ACE-I/D polymorphism and nicotine dependence in schizophrenia. Our results suggest that the ACE-I/D polymorphism may be relevant in determining the risk of nicotine dependence in female patients with schizophrenia while the ACE genotype-smoking interaction does not contribute to the clinical expression of schizophrenia.


Assuntos
Peptidil Dipeptidase A/genética , Polimorfismo Genético , Esquizofrenia/complicações , Esquizofrenia/genética , Tabagismo/complicações , Tabagismo/genética , Adulto , Doença Crônica , Estudos de Coortes , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Prevalência , Escalas de Graduação Psiquiátrica , Esquizofrenia/epidemiologia , Esquizofrenia/terapia , Fatores Sexuais , Tabagismo/epidemiologia
4.
J Assist Reprod Genet ; 34(3): 365-371, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27987113

RESUMO

PURPOSE: The aim of this study was to investigate the potential association of matrix metalloproteinase 7 (MMP7) -181 A/G and MMP12 -82 A/G functional single nucleotide polymorphisms (SNP) with idiopathic recurrent spontaneous abortion (IRSA) in Slovenian reproductive couples. METHODS: A case-control study was conducted on 149 couples with 3 or more consecutive idiopathic spontaneous pregnancy loses and 149 women and men with at least 2 live births and no history of pregnancy complications. Genotyping of MMP7 -181 A/G and MMP12 -82 A/G SNPs was performed using polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: There were no statistically significant differences in the distribution of MMP7 -181 A/G and MMP12 -82 A/G genotype, allele, or haplotype frequencies between IRSA patients and controls, as well as patients' primary and secondary IRSA. We also found no association of MMP7 -181 A/G and MMP12 -82 A/G genotypes, alleles, and haplotypes with IRSA. CONCLUSIONS: We found no evidence to support the association between IRSA and MMP7 -181 A/G and MMP12 -82 A/G SNPs in Slovenian reproductive couples.


Assuntos
Aborto Habitual/genética , Aborto Espontâneo/genética , Predisposição Genética para Doença , Metaloproteinase 12 da Matriz/genética , Metaloproteinase 7 da Matriz/genética , Aborto Habitual/patologia , Aborto Espontâneo/patologia , Adulto , Alelos , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Gravidez
5.
Reprod Biomed Online ; 32(2): 237-46, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26673102

RESUMO

The insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin I-converting enzyme gene (ACE) has been extensively studied as a predisposing factor for idiopathic recurrent spontaneous abortion (IRSA). A case-control study including 149 women with ≥3 spontaneous abortions and 149 controls was performed to test the association of ACE I/D polymorphism with IRSA. A systematic review was conducted of previous case-control studies, with strict selection criteria for meta-analyses. We also aimed to evaluate the potential differences in summary estimates between studies defining IRSA as ≥2 and ≥3 spontaneous abortions. Genotyping was performed by PCR, and systematic review conducted using PubMed and Scopus. There was no association of the polymorphism with IRSA in Slovenian women. Sixteen case-control studies, showing substantial differences regarding IRSA definition and selection criteria for women were identified. Meta-analysis was performed and included four studies defining IRSA as ≥2 spontaneous abortions and the current study, which defined IRSA as ≥3 spontaneous abortions. Based on random effects model, meta-analysis conducted on 1192 patients and 736 controls showed no association with IRSA under dominant(DD+IDvsII) and recessive(DDvsID+II) genetic models. Well-designed studies are needed to evaluate the role of ACE I/D polymorphism in IRSA defined as ≥3 spontaneous abortions.


Assuntos
Aborto Habitual/genética , Mutação INDEL , Íntrons , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Alelos , Estudos de Casos e Controles , Medicina Baseada em Evidências , Feminino , Predisposição Genética para Doença , Variação Genética , Genótipo , Humanos , Gravidez , Eslovênia
6.
Neurol Sci ; 37(12): 1955-1959, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27568030

RESUMO

The activity of angiotensin-converting enzyme (ACE) has been increased in the blood and cerebrospinal fluid of multiple sclerosis (MS) patients. In addition, there has been suppression of disease development in experimental autoimmune encephalomyelitis after blockade of ACE. These findings suggest that ACE may play a role in the MS pathogenesis. Since the previous studies investigating the association between the insertion/deletion (I/D) polymorphism in intron 16 of the ACE gene and MS reported contradictory results, we performed a meta-analysis of four studies conducted in European populations of Slavic origin (1062 patients and 1067 controls) using the Comprehensive Meta-analysis 3.0 software. The results demonstrated that the ACE I/D polymorphism had no statistically significant association with an increased MS risk (all p ≥ 0.05) under all genetic comparison models: (1) allelic (D vs. I), (2) recessive (DD vs. ID + II), (3) dominant (DD + ID vs. II), and (4) additive (DD vs. ID vs. II). This meta-analysis indicates that the ACE I/D polymorphism is not associated with susceptibility to MS in Europeans of Slavic origin. Further studies with larger sample sizes from genetically different populations are warranted.


Assuntos
Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único/genética , Deleção de Genes , Estudos de Associação Genética/estatística & dados numéricos , Genótipo , Humanos
7.
Med Sci Monit ; 22: 2144-51, 2016 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-27332079

RESUMO

The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models.


Assuntos
Sobrecarga de Ferro/metabolismo , Ferro/metabolismo , Hepatopatias/metabolismo , Animais , Doença Crônica , Hemocromatose/metabolismo , Hepcidinas/metabolismo , Homeostase , Humanos , Fígado/metabolismo
8.
Am J Hum Biol ; 28(6): 837-845, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27279290

RESUMO

OBJECTIVES: The research objective of this study is to enlarge and deepen the Y chromosome research on the Croatian population and enable additional insights into the population diversity and historic events that shaped the current genetic landscape of Croatia and Southeastern Europe (SEE). MATERIALS AND METHODS: A high-resolution phylogenetic and phylogeographic analysis of 66 biallelic (SNPs) and 17 microsatellite (STRs) markers of the Y chromosome was performed using 720 Croatian samples. The obtained results were placed in a wider European context by comparison with ∼4450 samples from a number of other European populations. RESULTS: A high diversity of haplogroups was observed in the overall Croatian sample, and all typical European Y chromosome haplogroups with corresponding clinal patterns were observed. Three distinct genetic signals were identifiable in the Croatian paternal gene pool - I2a1b-M423, R1a1a1b1a*-M558, and E1b1b1a1b1a-V13 haplogroups. DISCUSSION: The analyses of the dominant and autochthonous I2a1b-M423 lineage (>30%) suggest that SEE had a significant role in the Upper Paleolithic, the R1a1a1b1a*-M558 lineage (19%) represents a signal from present day Slavic populations of Central Europe in the Croatian population, and the phylogeography of the E1b1b1a1b1a-V13 clade (around 9%) implies cultural diffusion of agriculture into Europe via the Balkan Peninsula. Am. J. Hum. Biol., 2016. © 2016 Wiley Periodicals, Inc. Am. J. Hum. Biol. 28:837-845, 2016. © 2016Wiley Periodicals, Inc.


Assuntos
Cromossomos Humanos Y/genética , Pool Gênico , Variação Genética , Filogenia , Croácia , Humanos , Ilhas , Masculino
9.
Am J Med Genet A ; 167(6): 1426-7, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25899858

RESUMO

In the March issue of the Journal in 2012, we reported on a girl with Langer-Giedion syndrome (LGS) phenotype and a 7.5 Mb interstitial deletion at 8q23.3q24.13, encompassing the EXT1, but not the TRPS1 gene. Recent discoveries have shown that heterozygous intragenic mutations or contiguous gene deletions including the RAD21 gene, which is located downstream of the TRPS1 gene, are the cause of Cornelia de Lange syndrome-4. Considering that the interstitial deletion in our patient included the RAD21 and 30 other RefSeq genes, we would like to suggest a revision of the diagnosis reported in our previous paper and compare our patient to other reported patients with Cornelia de Lange syndrome-4 caused by heterozygous deletions of chromosome 8q24. © 2015 Wiley Periodicals, Inc.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 8 , Proteínas de Ligação a DNA/genética , Deleção de Genes , Síndrome de Langer-Giedion/genética , Fatores de Transcrição/genética , Feminino , Humanos
10.
J Assist Reprod Genet ; 32(12): 1789-94, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26475697

RESUMO

PURPOSE: The vascular endothelial growth factor A (VEGFA) is crucial for normal vasculogenesis and angiogenesis during pregnancy, and alterations in the VEGFA gene expression were detected in women with idiopathic recurrent spontaneous abortion (IRSA) and spontaneously aborted conceptuses. Our aim was to evaluate whether there is an association between the functional -2549 insertion/deletion (I/D) polymorphism in the promoter region of the VEGFA gene and IRSA in reproductive couples. METHODS: We performed a case-control study involving 149 women and their 140 partners with three or more IRSA and 149 control women and men. Allele-specific polymerase chain reaction was used for genotyping. RESULTS: We found no association of the -2549 I/D polymorphism with IRSA in women. However, men with the DD genotype have a 1.75-fold increased risk of IRSA compared with men carrying the ID and II genotypes (95 % confidence interval (CI) = 1.05-2.93, P = 0.032). In addition, the D allele in men contributes to a 1.42-fold increased risk of IRSA (95 % CI = 1.02-1.97, P = 0.036) compared to men carrying the I allele. CONCLUSIONS: Our results indicate that the -2549 I/D polymorphism in the VEGFA gene in men might be associated with IRSA. Additional genetic association studies including both partners, as well as expression studies, are needed to elucidate the role of this polymorphism in IRSA.


Assuntos
Aborto Habitual/genética , Mutação INDEL , Fator A de Crescimento do Endotélio Vascular/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Polimorfismo Genético , Eslovênia
11.
Coll Antropol ; 38(4): 1179-86, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25842753

RESUMO

This survey was performed to determine the relationship between the adherence to hypertension drug treatment and the perception of stress, depression, hypertension, and myocardial infarction. 300 patients with uncomplicated hyperten- sion from Rijeka, Croatia, were included (131 women, 169 men, mean age 53.5 years). Adherence to hypertension drug treatment as criterion, and the perception of stress, depression hypertension and myocardial infarction as prediclors were determined by self-assessment. Collected data were analysed using factor analysis, regression analysis, Kolmogorov-Smirnov test, chi2-test and t-test. The statistical significance was set at a probability rate of less than 5% (p < 0.05). 45.09% of women (p=0.479), and 64.08% of men (p = 0.032) were motivated to take antihypertensives. 55.79% of women (p = 0.382) and 64.78% of men (p = 0.028) had sufficient knowledge about drug treatment of hypertension. The positive predictors of motivation for taking antihypertensives were physiological disturbances and perceived potency of hypertension and the negative were perceived helplessness in stress control and negative thoughts and emotions. The positive predictors of knowledge about taking antihypertensives were perceived helplessness in stress control, perceived potency of hypertension and myocardial infarction and the negative predictors were perceived self-efficacy in stress control, physiological disturbances and evaluation of hypertension. Both the motivation as well as the knowledge about taking antihypertensives should be improved, especially in women. The perception of stress, depression, hypertension and myocardial infarction can be used to predict adherence to hypertension drug treatment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Depressão , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/psicologia , Cooperação do Paciente , Estresse Psicológico , Feminino , Humanos , Hipertensão/psicologia , Masculino
12.
Genes (Basel) ; 15(2)2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38397244

RESUMO

Parkinson's disease is a neurological disorder that affects motor function, autonomic functions, and cognitive abilities. It is likely that both genetic and environmental factors, along with age, contribute to the cause. However, there is no comprehensive guideline for genetic testing for Parkinson's disease, and more research is needed to understand genetic variations in different populations. There has been no research on the genetic background of Parkinson's disease in Croatia so far. Therefore, with the GiOPARK project, we aimed to investigate the genetic variants responsible for Parkinson's disease in 153 Croatian patients with early onset, familial onset, and sporadic late-onset using whole-exome sequencing, along with multiplex ligation-dependent probe amplification and Sanger sequencing in select patients. We found causative variants in 7.84% of the patients, with GBA being the most common gene (4.58%), followed by PRKN (1.96%), ITM2B (0.65%), and MAPT (0.65%). Moreover, variants of uncertain significance were identified in 26.14% of the patients. The causative variants were found in all three subgroups, indicating that genetic factors play a role in all the analyzed Parkinson's disease subtypes. This study emphasizes the need for more inclusive research and improved guidelines to better understand the genetic basis of Parkinson's disease and facilitate more effective clinical management.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/genética , Doença de Parkinson/epidemiologia , Croácia , Testes Genéticos , Sequenciamento do Exoma
13.
Med Sci Monit ; 19: 846-51, 2013 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-24113849

RESUMO

BACKGROUND: Lung cancer is the most common second primary cancer. We investigated whether the TNF-alpha-308 and TNF-alpha-238 polymorphisms were associated with the susceptibility and severity of lung cancer as the second primary cancer (LC2). MATERIAL/METHODS: This study included 104 patients from the group LC2. The control subjects included 2 groups. The first control group (LC1) comprised 201 unrelated patients with lung cancer as a first primary cancer. The second control group (HC) comprised 230 healthy blood donors, matched for sex and age to the study group. RESULTS: The frequencies of the TNF-alpha-238 polymorphism GG genotype and the G allele were higher in the LC2 group than in the LC1 group, but the differences did not reach significance (p=0.054 and p=0.057, respectively). Similar differences were found in the TNF-alpha-238 polymorphism GG genotype and G allele between the LC2 group and the HC group (p=0.054 and p=0.057, respectively). In terms of the different types of lung cancer, patients with a second primary NSCLC (non-small cell lung cancer) more frequently had TNF-alpha-238 polymorphism GG genotypes and G alleles than patients with a first primary NSCLC (the differences approached statistical significance: p=0.060, p=0.064, respectively). All (100%) patients of group LC2 (n=104) had the GG genotype and the G allele. GG genotype was exclusive and no A allele was found in group LC2. CONCLUSIONS: TNF-alpha-238 polymorphism GG genotype and the G allele could have a promotional effect on the development of NSCLC in the group of patients with LC2.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Segunda Neoplasia Primária/genética , Fator de Necrose Tumoral alfa/genética , Idoso , Idoso de 80 Anos ou mais , Croácia , Feminino , Frequência do Gene , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética
14.
J Reprod Med ; 58(3-4): 132-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23539881

RESUMO

OBJECTIVE: To test the association between insulinlike growth factor 2 (IGF2) ApaI and IGF2 receptor (IGF2R) Gly1619Arg gene polymorphisms and idiopathic male infertility. STUDY DESIGN: Polymerase chain reaction and restriction fragment length polymorphism methods were performed to detect the IGF2 ApaI and IGF2R Gly1619Arg genotypes in 98 Croatian men with idiopathic infertility and 113 fertile men. RESULTS: There were no significant differences between patients and controls according to genotype (chi2(IGF2) = 3.46, p = 0.177; chi2(IGF2R) = 1.12, p= 0.571, respectively) and allele frequencies (chi2(IGF2) = 3.23, p = 0.072; chi2(IGF2R) = 0.99, p = 0.319, respectively). Odds ratios for recessive, dominant and codominant models and association testing with each genotype combination revealed no difference between infertile men and controls. CONCLUSION: In this study we have shown that IGF2 ApaI and IGF2R Gly1619Arg gene polymorphisms are not associated with male infertility.


Assuntos
Infertilidade Masculina/genética , Fator de Crescimento Insulin-Like II/genética , Polimorfismo de Nucleotídeo Único , Receptor IGF Tipo 2/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Croácia , Frequência do Gene , Genes Dominantes , Genes Recessivos , Genótipo , Humanos , Masculino , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição
15.
Genes (Basel) ; 14(8)2023 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-37628665

RESUMO

Mitochondrial DNA (mtDNA) has been used for decades as a predominant tool in population genetics and as a valuable addition to forensic genetic research, owing to its unique maternal inheritance pattern that enables the tracing of individuals along the maternal lineage across numerous generations. The dynamic interplay between evolutionary forces, primarily genetic drift, bottlenecks, and the founder effect, can exert significant influence on genetic profiles. Consequently, the Adriatic islands have accumulated a subset of lineages that exhibits remarkable absence or rarity within other European populations. This distinctive genetic composition underscores the islands' potential as a significant resource in phylogenetic research, with implications reaching beyond regional boundaries to contribute to a global understanding. In the initial attempt to expand the mitochondrial forensic database of the Croatian population with haplotypes from small isolated communities, we sequenced mitogenomes of rare haplogroups from different Croatian island and mainland populations using next-generation sequencing (NGS). In the next step and based on the obtained results, we refined the global phylogeny of haplogroup N1a, HV2, and X by analyzing rare haplotypes, which are absent from the current phylogenetic tree. The trees were based on 16 novel and 52 previously published samples, revealing completely novel branches in the X and HV2 haplogroups and a new European cluster in the ancestral N1a variant, previously believed to be an exclusively African-Asian haplogroup. The research emphasizes the importance of investigating geographically isolated populations and their unique characteristics within a global context.


Assuntos
Genoma Mitocondrial , Humanos , Filogenia , Croácia , Genoma Mitocondrial/genética , Mitocôndrias/genética , DNA Mitocondrial/genética
16.
Am J Med Genet A ; 158A(3): 659-63, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22315192

RESUMO

Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 8 , Proteínas de Ligação a DNA/genética , Deleção de Genes , Síndrome de Langer-Giedion/genética , Fatores de Transcrição/genética , Hibridização Genômica Comparativa , Feminino , Humanos , Fenótipo , Proteínas Repressoras
17.
Reprod Biomed Online ; 24(5): 567-75, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22406112

RESUMO

Idiopathic recurrent spontaneous abortion (IRSA) has been associated with abnormalities in the remodelling of endometrial extracellular matrix, as well as aberrant matrix metalloproteinase (MMP) gene expression in endometrium of IRSA women and chorionic villi of IRSA concept. This study investigated the association of five functional MMP gene promoter polymorphisms (MMP1 -1607 1G/2G, MMP2 -735 C/T, MMP2 -1306 C/T, MMP3 -1612 5A/6A and MMP9 -1562 C/T) with IRSA. A total of 149 couples with at least three consecutive IRSA and 149 fertile couples were included in a case-control study. Genotype analysis was performed using PCR restriction fragment length polymorphism. Statistically significant differences were found in distributions of MMP2 -735 CT (chi-squared 10.21, P=0.006; OR 2.15, 95% CI 1.34-3.45, P=0.001), and MMP9 -1562 CC (chi-squared 9.06, P=0.010; OR 2.21, 95% CI 1.30-3.80, P=0.004) between IRSA women and controls. Combined analysis of MMP gene polymorphisms did not increase their predictive value. There were no statistically significant differences in genotype and allele frequencies of any polymorphism between IRSA men and controls. MMP2 -735 C/T and MMP9 -1562 C/T functional gene polymorphisms might be associated with an increased risk of IRSA in women. Considering the insufficient knowledge on genetic contribution to pregnancy loss, studies on genetic causes of idiopathic recurrent spontaneous abortion (IRSA) are of great importance. Development of a histologically and functionally normal endometrium is critical for subsequent endometrial decidualization, receptivity and implantation. The proper communication and interaction between maternal decidual cells and the embryo is essential for the establishment of a functional fetal-maternal interface. IRSA has been associated with abnormalities in the remodelling of endometrial extracellular matrix, as well as aberrant matrix metalloproteinase (MMP) gene expression in endometrium of IRSA women and chorionic villi of IRSA concepti. The aim of this study was to investigate the association of five functional MMP gene promoter polymorphisms with IRSA. A total of 149 couples with at least three consecutive IRSA and 149 fertile couples were included in a case-control study. Genotype analysis was performed using polymerase chain reaction and restriction fragment length polymorphism. Statistically significant differences were found in distribution of MMP2 -735 CT and MMP9 -1562 CC genotypes between IRSA and control women. Combined analysis of MMP gene polymorphisms did not increase their predictive value. There were no statistically significant differences in distribution of genotype and allele frequencies of any polymorphism between IRSA men and controls. Our results demonstrate that MMP2 -735 C/T and MMP9 -1562 C/T functional gene polymorphisms might be associated with an increased risk of IRSA in women.


Assuntos
Aborto Habitual/genética , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo de Nucleotídeo Único/genética , Aborto Habitual/epidemiologia , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gravidez , Fatores de Risco
18.
Mol Biol Rep ; 39(3): 2253-8, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21643746

RESUMO

The aim of this study was to investigate the possible influence of hemochromatosis gene mutations (HFE-C282Y and H63D) and transferrin gene C2 variant (TF-C2) on susceptibility to schizophrenia and schizoaffective disorder and/or age at first hospital admission. Genotyping was performed in 176 Croatian patients and 171 non-psychiatric Croatian controls using PCR-RFLP analyses. Regarding the H63D mutation, allele and genotype frequencies reached boundary statistical significance. Other allele and genotype distributions were not significantly different between two groups. We also analyzed age at first hospital admission as a continuous variable using the non-parametric Mann-Whitney U-test and Kruskal-Wallis test, and multiple regression analysis. The results of these tests were negative. We concluded that investigated HFE mutations and TF-C2 variant are not high-risk genetic variants for schizophrenia/schizoaffective disorder in our population. Also our data do not support their impact on age at onset of the first psychotic symptoms.


Assuntos
Predisposição Genética para Doença/genética , Antígenos de Histocompatibilidade Classe I/genética , Proteínas de Membrana/genética , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/genética , Esquizofrenia/epidemiologia , Esquizofrenia/genética , Transferrina/genética , Adulto , Idade de Início , Croácia/epidemiologia , Feminino , Estudos de Associação Genética , Genótipo , Proteína da Hemocromatose , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Genético/genética , Polimorfismo de Fragmento de Restrição , Análise de Regressão , Estatísticas não Paramétricas
19.
Coll Antropol ; 36(3): 745-54, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23213927

RESUMO

Metabolic syndrome presents a significant public health problem today, in Croatia as well as the rest of the world, considering the fact that the World Health Organization classifies its diagnostic criteria, such as high blood pressure and obesity, among ten major risk factors for health. The research of the prevalence of metabolic syndrome among the inhabitants of the island of Cres included a total of 385 adult subjects, 249 women and 136 men. The incidence of metabolic syndrome in two subpopulations of the inhabitants: the inhabitants of the town of Cres (urban population) and the inhabitants of other settlements (rural population), was analysed. The incidence of metabolic syndrome among the inhabitants of the island of Cres was determined according to definitions of the WHO (World Health Organization) and the NCEP-ATP III program (National Cholesterol Education Program-Third Adult Treatment Panel III). It was established that the overall prevalence of metabolic syndrome on the island of Cres was 14% according to the WHO definition (20.6% in men and 10.4% in women) and 24.9% according to the NCEP-ATP III definition (33.1% in men and 20.5% in women). The study also showed that the prevalence of risk factors for developing metabolic syndrome and complex diseases was much higher among the subjects from other settlements than among the subjects from the town of Cres, a consequence of age and a lifestyle with lack of physical activity.


Assuntos
Síndrome Metabólica/epidemiologia , População Urbana/estatística & dados numéricos , Adulto , Idoso , Croácia/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Masculino , Ilhas do Mediterrâneo/epidemiologia , Pessoa de Meia-Idade , Prevalência
20.
Coll Antropol ; 36(2): 363-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22856216

RESUMO

The aim of this research was to investigate the prevalence of obesity and high blood pressure and to prove which of three anthropometric indicators of obesity - waist circumference, body mass index (BMI) waist-to-hip ratio - is better predictor for the development of hypertension in women population of the island of Cres. We approached separately groups of women with measured high blood pressure and with previously diagnosed. The research was preformed within the research project "Genetic and biomedical characteristics of the population of the island of Cres". This was the cross sectional study and data were obtained on the sample of 247 females over 18 years old that voluntarily participated in this study. In our study group the prevalence of overweight was 39.0%, obesity 27.5%, increased waist circumference was present in 69.4% while increased blood pressure was found in 53.0% examinees. Our results indicate that age, BMI, impaired glucose concentration and serum cholesterol could be considered as predictors for the development of arterial hypertension, whether measured or previously diagnosed.


Assuntos
Antropometria/métodos , Índice de Massa Corporal , Hipertensão/epidemiologia , Circunferência da Cintura , Relação Cintura-Quadril , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/epidemiologia , Valor Preditivo dos Testes , Fatores de Risco , Adulto Jovem
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