Estrogen receptor 1 gene (TA)n polymorphism is associated with lone atrial fibrillation in men

Aim To determine the association between the number of thymine-adenine (TA)n dinucleotide repeats in the promoter region of the gene coding for the estrogen receptor alpha (ESR1) and the prevalence of lone atrial fibrillation (AF) in men. Methods We conducted a case-control study involving 89 men with lone AF and 166 healthy male controls. The ESR1 genotype was established by polymerase chain reaction and capillary electrophoresis. To assess the association of ESR1 genotype with AF, logistic regression models were built with AF as outcome. Results Men with lone AF had significantly greater number of (TA)n repeats of single alleles than controls (mean ± standard deviation, 19.2 ± 4.2 vs 18 ± 4.3, P = 0.010). After adjustment for other factors, a unit-increase in (TA)n repeat number was associated with a significantly greater likelihood of AF (odds ratio 1.069; 95% confidence interval 1.024-1.116, P = 0.002). Conclusions Our results indicate that a greater number of (TA)n repeats in the promoter region of ESR1 is associated with a significantly increased likelihood of lone atrial fibrillation in men

Association of Angiotensin-Converting Enzyme Insertion-Deletion Polymorphism with Preeclampsia

The aim of this study was to determine if insertion-deletion polymorphism of angiotensin-converting enzyme is a risk factor for the development of preeclampsia. Sixty women with preeclampsia and 50 normotensive pregnant women were included in this study. Preeclampsia was defined as blood pressure > 140/90 mmHg in a previously normotensive women with proteinuria >300 mg/L in a 24-hours. Twelve women also had preeclampsia in previous pregnancy. The genotyping of polymorphism in the intron 16 of the angiotensin-converting enzyme was performed by the polymerase chain reaction followed by the agarose electrophoresis. The patients were divided into three groups according to the presence (I) or absence (D) of insertional polymorphism (II, ID, and DD). Genotype distribution and allele frequencies were compared by Mantel-Haenszel c 2 testing. The frequency of DD genotype was not significantly higher in women with preeclampsia (26/60)than in the control group (14/50, p=0.096). The D allele frequency was significantly higher in 17 women with preeclampsias who required delivery before 34 weeks of pregnancy (0.735), than in 43 women in whom obstetric complications took place after 34 weeks of pregnancy (0.56, p=0.036). The D allele frequency was 0.83 in women having recurrent preeclampsia, i.e. significantly higher compared with women, who were for the first time, experienced preeclampsia (0.57, p=0.013). This study showed a significantly positive association between D allele frequency and risk of recurrent preeclampsia and preterm delivery before 34 weeks of pregnancy. The deletion genotype could be an important contributing factor for an early onset and recurrent preeclampsia

Povezanost apolipoproteina E ε2 s kasnijim početkom epilepsije temporalnog režnja

The aim of the study was to evaluate the possible association between Apo E polymorphisms and age at seizure onset in patients with non-lesional temporal lobe epilepsy. Eighty patients with non-lesional temporal lobe epilepsy with or without bilateral tonic-clonic propagation were analyzed. Age at seizure onset was defined as age at the first unequivocal seizure (excluding febrile convulsions). ApoE alleles were determined by a procedure where genome DNA was amplified by chain reaction along with polymerase, using the LightCycler kit (Roche) for ApoE mutations on codons 112 and 158. There was a statistically significant difference between the groups of patients with ApoE ε2/3 and ε3/4 genotypes (p=0.03), but not between patients with ApoE ε2/3 and ε3/3, and those with ApoE ε3/4 and ε3/3. In conclusion, the results of our study suggested positive association of a specific ApoE genotype and onset of non-lesional temporal lobe epilepsy.Cilj ovoga istraživanja bio je utvrditi moguću povezanost genskog polimorfizma ApoE s dobno ranijim početkom bolesti kod bolesnika s epilepsijom temporalnog režnja i negativnim nalazom magnetske rezonancije mozga. U istraživanje je bilo uključeno 80 bolesnika s epilepsijom temporalnog režnja i negativnim nalazom magnetske rezonancije mozga. Dob početka bolesti definirana je kao dob pojavnosti prvog neprovociranog epilepsijskog napadaja (isključujući febrilne konvulzije). ApoE aleli su određeni postupkom pri kojem je genomska DNA amplificirana lančanom reakcijom uz polimerazu, a korišten je detekcijski kit LightCycler (Roche) za mutacije ApoE na kodomu112 i 158. Utvrđena je značajna statistička razlika između skupina bolesnika s genotipom ApoE ε2/3 i ε3/4 (p=0,03), dok između bolesnika s ApoE ε2/3 i ε3/3 i onih s ApoE ε3/4 i ε3/3 nije bilo značajne statističke razlike. Rezultati istraživanja ukazuju na moguću povezanost specifičnog genotipa ApoE i dobi početka bolesti kod bolesnika s epilepsijom temporalnog režnja i negativnim nalazom magnetske rezonancije mozga

Interaction of genetic risk factors confers increased risk for metabolic syndrome: the role of peroxisome proliferator-activated receptor γ

AIM: The aim of the study was to estimate the influence of interactions between peroxisome proliferator-activated receptor γ (PPARγ) and target genes lipoprotein lipase (LPL), interleukin 6 (IL6), angiotensin converting enzyme (ACE), and angiotensin II type 1 receptor (AT1R) on metabolic syndrome (MetSy) and its traits. ----- METHODS: The study included 527 participants (263 with MetSy and 264 controls). Genotyping of PPARγ Pro12Ala, LPL PvuII (-/+), IL6 -174G>C, ACE I/D and AT1R 1166A>C was performed using polymerase chain reaction-restriction fragment length polymorphism-based methods. ----- RESULTS: Interaction between PPARγ Pro12Ala and LPL Pvu(-/+) improved prediction of MetSy over and above prediction based on a model containing no interactions (χ(2)=7.22; df=1; p=0.007). In the group of participants with PPARγ Pro12Ala or Ala12Ala genotypes, those with the LPL Pvu (-/+) or (+/+) genotype had greater odds for MetSy (odds ratio OR=5.98; 95% confidence interval CI: 1.46-24.47, p=0.013). Interaction between PPARγ Pro12Ala and IL6 -174G>C improved prediction of high fasting blood glucose (χ(2)=13.99; df=1; p<0.001). PPARγ Ala12 variant was found protective in patients with IL6 -174GG genotype (OR=0.10; 95% CI: 0.02-0.57, p=0.01), while in the case of IL6 -174C allele carriers, for PPARγ Ala12 carriers, larger odds for high glucose levels compared with Pro12 variant were observed (OR=2.39; 95% CI: 1.11-5.17, p=0.026). Interactions of PPARγ and ACE were significant for BMI. In the group with ACE DD genotype, those with PPARγ Pro12Ala or Ala12Ala genotype have greater odds for obesity (OR=9.98; 95% CI: 1.18-84.14, p=0.034). ----- CONCLUSIONS: PPARγ gene variants can, in interaction with some of its target genes, modulate physiological processes leading to the development of MetSy

SIGNIFICANCE OF NEONATAL SCREENING FOR CYSTIC FIBROSIS

Cistična fibroza (CF) je autosomno recesivno nasljedna bolest i smatra se najčešćom smrtonosnom bolešću u bijele rase. Dijagnostički pristup bolesti temelji se na dijagnostičkom konsenzusu po kojem se sumnja na CF može ¬postaviti među ostalim i na osnovi pozitivnog nalaza novorođenačkog probira. Dok je u svijetu zadnjih godina sve više djece koja se otkrivaju u programu novorođenačkog probira, u Hrvatskoj se on ne provodi. Bolesnici u kojih se dijagnoza postavi nakon novorođenačkog probira imaju neke prednosti, rizike ali i nove probleme, te izazove za medicinsku struku s kojima se nismo susretali u dosadašnjoj praksi. Prednost probira najviše se očituje u boljoj uhranjenosti i boljem potencijalu kognitivnih funkcija te u izbjegavanju komplikacija koje su posljedica malnutricije. Prednost glede očuvanja plućne funkcije sadrži više kontroverza. Rano prepoznavanje bolesti često dovodi do ranog izlaganja bolesnika riziku ¬infekcija Pseudomonasom zbog odlaska u ustanove u kojima susreće druge bolesnike s CF. Poznavanje prednosti i rizika novorođenačkog probira na CF omogućuje procjenu njegove važnosti ne samo za bolesnika ili njegovu obitelji već i za čitavu zajednicu.Cystic fibrosis is among Caucasians the most common lethal autosomal recessive inherited disease. Diagnosis is based on meeting the criteria published as an expert consensus. Neonatal screening is one of the mentioned criteria. The number of children diagnosed with cystic fibrosis through neonatal screening is increasing throughout the world, but is not performed in Croatia. Early identification of these patients carries some advantages and some risks, posing new challenges for health workers. The most pronounced advantage is better growth and cognitive potentials for screened children, as well as less complications arising from malnutrition. Benefits regarding preservation of lung function are more controversial. Detection of patients through screening programs often means early exposure to Pseudomonas infections due to contacts with other CF patients in specialized centers. Recognizing potential advantages and risks of neonatal screening programs for CF brings new knowledge not only for individual patients and their families, but for the entire community

Abnormal motoneuron migration, differentiation, and axon outgrowth in spinal muscular atrophy

The role of heterotopic (migratory) motoneurons (HMN) in the pathogenesis of spinal muscular atrophy (SMA) is still controversial. We examined the occurrence and amount of HMN in spinal cord tissue from eight children with SMA (six with SMA-I and two with SMA-II). All affected subjects were carrying a homozygous deletion of exon 7 in the SMN1 gene. Unlike controls, virtually free from HMN, all SMA subjects showed a significant number of HMN at all levels of the spinal cord. Heterotopic neurons were hyperchromatic, located mostly in the ventral white matter and had no axon or dendrites. More than half of the HMN were very undifferentiated, as judged from their lack of immunoreactivity for NeuN and MAP2 proteins. Small numbers of more differentiated heterotopic neurons were also found in the dorsal and lateral white matter region. As confirmed by ultrastructural analysis, in situ end labeling (ISEL) and CD68 immunoreactivity, HMN in the ventral outflow were found to have no synapses, to activate microglial cells, and to eventually die by necrosis. An unbiased quantitative analysis showed a significant negative correlation between age of SMA subjects (a reflection of the clinical severity) and the number of HMN. Subjects who died at older ages had increased number of GFAP-positive astrocytes. Complementing our previous report on motoneuron apoptosis within the ventral horns in SMA, we now propose that abnormal migration, differentiation, and lack of axonal outgrowth may induce motoneuron apoptosis predominantly during early stages, whereas a slower necrosis-like cell death of displaced motoneurons which "escaped" apoptosis characterizes later stages of SMA

Interactions of MinK and e-NOS Gene Polymorphisms Appear to Be Inconsistent Predictors of Atrial Fibrillation Propensity, but Long Alleles of ESR1 Promoter TA Repeat May Be a Promising Marker

Interactions of MinK and e-NOS Gene Polymorphisms Appear to Be Inconsistent Predictors of Atrial Fibrillation Propensity, but Long Alleles of ESR1 Promoter TA Repeat May Be a Promising Marker. We analyzed minK, e-NOS and ESR1 gene polymorphisms in 40 patients with atrial fibrillation (AF) without major structural heart disease compared to 35 healthy controls. A missense polymorphism in the minK gene with A/G substitution at nucleotide 112 causing serine (S) to glycine (G) change, 786 T/C polymorphism in the 5’ flanking region of e-NOS gene and TA polymorphism in the regulatory region of estrogen receptor ESR1 gene with long (ł19 TA repeats) and short alleles were examined. Only a slight increase in minK G allele frequency, but with marked excess in AG/TT combination of minK and e-NOS polymorphisms was found in the AF group. The interpretation remains tentative due to small groups precluding statistical significance of differences, possible lab flaws and inconsistencies with earlier data. However, ESR1 long allele homozygotes were strikingly more frequent in the AF than in control group, reaching statistical significance surprisingly in males (p<0.02). Functional activity of estrogen receptors may be more critical in males than in females with abundance of circulating estrogen. Contrasting the intricate complexity of genetic polymorphisms influencing cardiac rhythm with our modest research, we would limit the conclusion to the plea for further research of ESR1 role in AF