Intron polymorphism
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Monoaminooxidáza B (MAO-B) je enzym, který se účastní metabolismu dopaminu, benzylaminu, fenylethylaminu, tyraminu a tryptaminu. Aktivita enzymu MAO-B byla již vícekrát asociována s některými psychickými poruchami, mimo jiné i s afektivními poruchami. Polymorfismus A/G v intronu 13. genu pro MAO-B ovlivňuje variabilitu aktivity enzymu MAO-B. Cílem této studie bylo zjistit, zda existuje vztah mezi tímto polymorfismem genu pro MAO-B a intenzitou pooperační bolesti. Testovali jsme celkem 284 osob (105 mužů a 179 žen), které se podrobily plánované tonzilektomii. Pro detekci polymorfismu byla použita metoda řetězové polymerázové reakce (PCR) s alelově specifickými primery. Bolest byla měřena pomocí vizuální analogové škály VAS. V naší práci jsme ve skupině mužů objevili vztah mezi polymorfismem A/G v intronu 13 genu pro MAO-B a průměrnou intenzitou pooperační bolesti. Zjistili jsme statisticky významně vyšší průměrnou intenzitu pooperační bolesti u mužů s alelou G ve srovnání s muži s alelou A. Výsledky naší studie naznačují vztah mezi polymorfismem genu pro MAO-B a průměrnou intenzitou pooperační bolesti u mužů České republiky. Možná role MAO-B ve vnímání intenzity bolesti je diskutována především v souvislosti s vlivem MAO-B na psychickou náladu.
The monoamine oxidase B (MAO-B) is an enzyme involved in the metabolism of dopamine, benzylamine, phenylethylamine, tyramine and tryptamine. MAO-B activity was associated many times with some psychiatric diseases including affective disorders. The A/G polymorphism in intron 13 of the MAO-B gene was previously associated with a variability of the MAO-B enzyme activity. The aim of the present association study was to examine the relationship between the A/G polymorphism in intron 13 and postoperative pain intensity. We examined 284 subjects (105 males and 179 females) that underwent planned tonsillectomy. PCR method with allele specific primers for the detection of A/G polymorphism was used. The intensity of pain was tested by visual analogue scale (VAS). We found a relationship between the A/G polymorphism in intron 13 of the MAO-B gene and average intensity of postoperative pain in male subjects. We found statistically significantly higher average intensity of postoperative pain in males with G allele in comparison with males with A allele. Results of our study indicate the relationship between the MAO-B polymorphism and postoperative pain intensity in Czech male population. The potential role of the MAO-B in feeling of pain intensity is discussed mainly in the context of the influence of MAO-B on the mood.
- MeSH
- DNA genetika MeSH
- estrogeny krev MeSH
- finanční podpora výzkumu jako téma MeSH
- genotyp MeSH
- lidé MeSH
- měření bolesti metody MeSH
- monoaminoxidasa fyziologie genetika krev MeSH
- polymorfismus genetický MeSH
- pooperační bolest etiologie farmakoterapie genetika MeSH
- tonzilektomie metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
To date, polymorphisms in several genes have been associated with a strength/power performance including alpha 3 actinin, ciliary neurotrophic factor, vitamin D receptor, or angiotensin I converting enzyme, underlining the importance of genetic component of the multifactorial strength/power-related phenotypes. The single nucleotide variation in peroxisome proliferator-activated receptor alpha gene (PPARA) intron 7 G/C (rs4253778; g.46630634G>C) has been repeatedly found to play a significant role in response to different types of physical activity. We investigated the effect of PPARA intron 7 G/C polymorphism specifically on anaerobic power output in a group of 77 elite male Czech ice hockey players (18-36 y). We determined the relative peak power per body weight (Pmax.kg(-1)) and relative peak power per fat free mass (W.kg(-1)FFM) during the 30-second Wingate Test (WT30) on bicycle ergometer (Monark 894E Peak bike, MONARK, Sweden). All WT30s were performed during the hockey season. Overall genotype frequencies were 50.6% GG homozygotes, 40.3% CG heterozygotes, and 9.1% CC homozygotes. We found statistically significant differences in Pmax.kg(-1) and marginally significant differences in Pmax.kg(-1)FFM values in WT30 between carriers and non-carriers for C allele (14.6 ± 0.2 vs. 13.9 ± 0.3 W.kg(-1) and 15.8 ± 0.2 vs. 15.2 ± 0.3 W.kg(-1)FFM, P = 0.036 and 0.12, respectively). Furthermore, Pmax.kg(-1)FFM strongly positively correlated with the body weight only in individuals with GG genotypes (R = 0.55; p<0.001). Our results indicate that PPARA 7C carriers exhibited higher speed strength measures in WT30. We hypothesize that C allele carriers within the cohort of trained individuals may possess a metabolic advantage towards anaerobic metabolism.
- MeSH
- anaerobióza MeSH
- dospělí MeSH
- frekvence genu MeSH
- genotyp MeSH
- introny genetika MeSH
- jednonukleotidový polymorfismus * MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- PPAR alfa genetika MeSH
- sportovní výkon * MeSH
- tělesná hmotnost genetika MeSH
- zátěžový test * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: High extracellular calcium concentration (Cao(2+)) acts to inhibit calcium sensing receptor (CaR) signalling on cellular surfaces in parathyroid glands. This receptor is, however, also expressed on the membranes of some non-calciotropic endocrine cells, including pituitary-derived cells. The aim of our study was to analyse relationships between the CaR gene and the circulating FSH and LH in normal post-menopausal women. METHODS: A total of 95 untreated euparathyroid post-menopausal women were investigated in the study. The serum FSH and LH levels were evaluated in relationship to allele combinations of the CaR gene (C/T polymorphism in the intron 5 and A986S polymorphism in exon 7), using an analysis of co-variance (ANCOVA) model. RESULTS: Distribution of TT, TC and CC allele combinations (intron 5 C/T polymorphism) was 51, 43 and 6 %, respectively. Higher serum FSH and LH levels were found in carriers of C allele than in women without this allele (p < 0.002 and p < 0.03, respectively). No correlations were found between A986S polymorphism and serum FSH and LH levels. CONCLUSIONS: Serum FSH and LH levels are associated with intron 5 C/T (but not A986S) polymorphism of the CaR gene in untreated post-menopausal women. The physiological role of the CaR gene in the regulation of the gonadotropic function needs to be further investigated.
- MeSH
- alely MeSH
- dospělí MeSH
- financování organizované MeSH
- folikuly stimulující hormon krev MeSH
- genotyp MeSH
- introny MeSH
- lidé MeSH
- luteinizační hormon krev MeSH
- polymorfismus genetický MeSH
- postmenopauza MeSH
- průřezové studie MeSH
- receptory "calcium-sensing" genetika metabolismus MeSH
- statistika jako téma MeSH
- vápník metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- ženské pohlaví MeSH
Protein tyrosine phosphatase, nonreceptor type 22 (PTPN22), is an archetypal non-HLA autoimmunity gene. It is one of the most prominent genetic contributors to type 1 diabetes mellitus outside the HLA region, and prevalence of its risk variants is subject to enormous geographic variability. Here, we address the genetic background of patients with type 1 diabetes mellitus of Armenian descent. Armenia has a population that has been genetically isolated for 3000 years. We hypothesized that two PTPN22 polymorphisms, rs2476601 and rs1310182, are associated with type 1 diabetes mellitus in persons of Armenian descent. In this association study, we genotyped the allelic frequencies of two risk-associated PTPN22 variants in 96 patients with type 1 diabetes mellitus and 100 controls of Armenian descent. We subsequently examined the associations of PTPN22 variants with the manifestation of type 1 diabetes mellitus and its clinical characteristics. We found that the rs2476601 minor allele (c.1858T) frequency in the control population was very low (q = 0.015), and the trend toward increased frequency of c.1858CT heterozygotes among patients with type 1 diabetes mellitus was not significant (OR 3.34, 95% CI 0.88-12.75; χ2 test p > 0.05). The control population had a high frequency of the minor allele of rs1310182 (q = 0.375). The frequency of c.2054-852TC heterozygotes was significantly higher among the patients with type 1 diabetes mellitus (OR 2.39, 95% CI 1.35-4.24; χ2 test p < 0.001), as was the frequency of the T allele (OR 4.82, 95% CI 2.38-9.76; χ2 test p < 0.001). The rs2476601 c.1858CT genotype and the T allele correlated negatively with the insulin dose needed three to six months after diagnosis. The rs1310182 c.2054-852CC genotype was positively associated with higher HbA1c at diagnosis and 12 months after diagnosis. We have provided the first information on diabetes-associated polymorphisms in PTPN22 in a genetically isolated Armenian population. We found only a limited contribution of the prototypic gain-of-function PTPN22 polymorphism rs2476601. In contrast, we found an unexpectedly close association of type 1 diabetes mellitus with rs1310182.
- MeSH
- diabetes mellitus 1. typu * genetika MeSH
- fosfatasy MeSH
- introny MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- tyrosinfosfatasa nereceptorového typu 22 genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Arménie MeSH
BACKGROUND/AIMS: Calcium-Sensing Receptor (CaSR) significantly affects calcium-phosphate metabolism in kidneys, and it is implicated in the pathogenesis of diabetes mellitus (DM) due to its expression in pancreatic β-cells. The role of CaSR as one of the players in pathogenesis of chronic kidney disease (CKD) has been speculated. METHODS: 158 Type 2 diabetic patients divided into three groups according to occurrence and type of kidney complications, 66 nondiabetic patients CKD, and 93 healthy subjects were enrolled into the study to analyze the role of two CaSR polymorphisms (in the codon 990 and in the intron 4) in ethiopathogenesis of DM and CKD. The Type 2 diabetic groups consisted of 48 patients without any kidney abnormalities, 58 patients with diabetic nephropathy (DN), and 52 patients with nondiabetic renal disease (NDRD). The distribution of genotype and allele frequencies was studied using PCR with the TaqMan Discrimination Assay or followed by the Restriction Fragment Length Polymorphism method, respectively. RESULTS: We have found that the intron 4 polymorphism is a risk factor for the development of DM and CKD, except DN, while the codon 990 does not show any disease association. CONCLUSION: We conclude that CaSR is a general factor in pancreas and kidney pathologies.
- MeSH
- chronická nemoc MeSH
- diabetes mellitus 2. typu diagnóza genetika MeSH
- diabetické nefropatie diagnóza genetika MeSH
- dospělí MeSH
- introny genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- komplikace diabetu diagnóza genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci ledvin diagnóza genetika MeSH
- receptory "calcium-sensing" genetika MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Alliinase is an important enzyme occurring in Allium species that converts precursors of sulfuric compounds, cysteine sulfoxides into a biologically active substance termed allicin. Allicin facilitates garlic defense against pests and produces health-promoting compounds. Alliinase is encoded by members of a multigene family that has not yet been sufficiently characterized, namely with regard to the copy numbers occurring within the genome and the polymorphisms among the family members. RESULTS: We cloned 45 full-length alliinase amplicons of cultivar (cv.) Jovan. Sequence analyses revealed nine different sequence variants (SVs), confirming the multilocus nature of this gene family. Several mutations in exons, mainly occurring in the first exon coding for vacuolar signal peptide, were found. These results enabled us to identify sequences with putatively modified vacuole-targeting abilities. We found additional sequence variants using partial amplicons. We estimated that the minimum number of gene copies in the diploid genome of the investigated cultivar was fourteen. We obtained similar results for another three cultivars, which differed in bolting type and place of origin. The further identification of high degree of polymorphisms in the intron regions allowed us to develop a specific polymerase chain reaction assay capable to capture intron length polymorphism (ILP). This assay was used to screen 131 additional accessions. Polymorphic data were used for cluster analysis, which separated the bolting and non-bolting garlic types and those with high cysteine-sulfoxide contents in a similar way as AFLP analysis in previous study. These newly developed markers can be further applied for the selection of desirable garlic genotypes. CONCLUSIONS: Detailed analysis of sequences confirmed multigenic nature of garlic alliinase. Intron and exon polymorphism analysis generated similar results as whole genome variability assessed previously by AFLP. Detected polymorphism is thus also associated with cysteine-sulphoxide content in individual genotypes. ILP markers capable to detect intron polymorphisms were newly developed. Developed markers could be applied in garlic breeding. Higher genetic variability found in bolting genotypes may indicates longer period of their sexual propagation in comparison with nonbolting genotypes.
The regulation of the human apolipoprotein (apo) B gene that plays a crucial role in lipid metabolism is apparently very complex, with multiple cis- and trans-acting regulatory factors. One of these factors is an enhancer region in the second intron. In this region a point mutation at position + 722 has been found that is detectable by the restriction enzyme StyI. The report of Levy-Wilson et al. (1991) could suggest that the mutant allele (abolished StyI site) is associated with hypocholesterolemia. To investigate further the possible effect of this mutation on plasma cholesterol levels, we have compared the frequency of the mutant allele between 206 hypercholesterolemic Norwegian or Czech subjects on one hand, and 165 hypocholesterolemic Norwegian or Czech subjects on the other hand. No significant difference in frequency was found between the hypercholesterolemic and the hypocholesterolemic groups. This finding indicates either that the mutation at position + 722 does not affect the enhancer activity or that this in vitro enhancer activity is of little or no clinical significance. One of the Norwegian hypercholesterolemic subjects who was of Czech descent possessed the apoB 3500 mutation that leads to defective binding of low density lipoprotein (LDL) to the LDL receptors. Haplotype analysis of the apoB gene in her family showed that the mutation-bearing allele was identical to that reported in other countries, indicating a common gene source.
- MeSH
- apolipoproteiny B * genetika MeSH
- bodová mutace MeSH
- cholesterol * nedostatek MeSH
- dítě MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetické markery MeSH
- haplotypy MeSH
- hypercholesterolemie * genetika MeSH
- introny * genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 2 MeSH
- molekulární sekvence - údaje MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- restrikční endonukleasy typu II MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- senioři MeSH
- zesilovače transkripce * genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Československo MeSH
- Norsko MeSH
The regulation of the human apolipoprotein (apo) B gene that plays a crucial role in lipid metabolism is apparently very complex, with multiple cis- and trans-acting regulatory factors. One of these factors is an enhancer region in the second intron. In this region a point mutation at position + 722 has been found that is detectable by the restriction enzyme StyI. The report of Levy-Wilson et al. (1991) could suggest that the mutant allele (abolished StyI site) is associated with hypocholesterolemia. To investigate further the possible effect of this mutation on plasma cholesterol levels, we have compared the frequency of the mutant allele between 206 hypercholesterolemic Norwegian or Czech subjects on one hand, and 165 hypocholesterolemic Norwegian or Czech subjects on the other hand. No significant difference in frequency was found between the hypercholesterolemic and the hypocholesterolemic groups. This finding indicates either that the mutation at position + 722 does not affect the enhancer activity or that this in vitro enhancer activity is of little or no clinical significance. One of the Norwegian hypercholesterolemic subjects who was of Czech descent possessed the apoB 3500 mutation that leads to defective binding of low density lipoprotein (LDL) to the LDL receptors. Haplotype analysis of the apoB gene in her family showed that the mutation-bearing allele was identical to that reported in other countries, indicating a common gene source.
- MeSH
- apolipoproteiny B genetika MeSH
- bodová mutace MeSH
- cholesterol nedostatek MeSH
- dítě MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetické markery MeSH
- haplotypy MeSH
- hypercholesterolemie genetika MeSH
- introny genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- lidské chromozomy, pár 2 MeSH
- molekulární sekvence - údaje MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus délky restrikčních fragmentů MeSH
- restrikční endonukleasy typu II MeSH
- sekvence nukleotidů MeSH
- sekvenční analýza DNA MeSH
- senioři MeSH
- zesilovače transkripce genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Československo MeSH
- Norsko MeSH
Pozadie problému: Inzerčno (I)/delečný (D) polymorfizmus lokalizovaný v intróne 16 génu pre angiotenzín-konvertujúci enzým (ACE) je asociovaný so zvýšeným rizikom rozvoja ochorení kardiovaskulárneho systému. Avšak jeho vzťah k pľúcnej hypertenzii nie je jasný. Predošlé práce ukázali, že u pacientov s primárnou pľúcnou hypertenziou sa vyskytuje ACE DD genotyp častejšie ako genotyp s neprítomnosťou D alely. Hypotéza: Predpokladáme, že pacienti s chronickou obštrukčnou chorobou pľúc (CHOCHP), ktorí sú nositeľmi D alely, majú vyššie riziko rozvoja pľúcnej hypertenzie. Pacienti a metódy: Súbor tvorilo 40 pacientov hospitalizovaných s diagnózou CHOCHP, u ktorých bolo zrealizované funkčné vyšetrenie pľúc použitím bodypletyzmografie, tlak v pľúcnici bol určený echokardiograficky. Na stanovenie genotypu v l/D polymorfizme génu pre ACE bola použitá polymerázová retazová reakcia (PCR). Výsledky: Echokardiograficky stanovené tlaky (stredný a systolický) v arteria pulmonalis boli signifikantne vyššie v skupine pacientov s DD a ID génovým polymorfizmom pre ACE oproti pacientom s genotypom II (15,2 ±1,6 oproti 8,8 ± 0,8 mm Hg, p < 0,01; 32,9 ± 2,5 oproti 21,6 ± 2,3 mm Hg, p < 0,05). V multivariátiiej lineárnej regresnej analýze boli I/D génový polymorfizmus pre ACE a FEVl jedinými nezávislými prediktormi tiakov v pľúcnici. Záver: Naše predbežné výsledky ukázali, že I/D génový polymorfizmus pre ACE má u pacientov s CHOCHP významný vztah k riziku rozvoja pľúcnej hypertenzie. K hlbšiemu poznaniu genetického rizika rozvoja pľúcnej hypertenzie bude potrebné uskutočniť v budúcnosti ďalšie sledovania na väčších súboroch pacientov.
Background: The insertion (1)/deletion (D) polymorphism at intion 16 of angiotensin-converting enzyme (ACE) gene has been associated with an increased risk of cardiovascular diseases, however, its relationship to pulmonary hypertension is unclear. However, the ACE DD genotype is more prevalent in patients with primary pulmonary hypertension than the non-DD genotype. Hypothesis: In patients with chronic obstructive pulmonary disease (COPD), the carriers of D allelle are at higher risk of developing pulmonary hypertension. Patients and methods: In 40 consecutive patients with COPD, lung function was assessed using bodyplethysmography, pulmonary artery pressures were determined using echocardiography. The ACE gene I/D polymorphism was detected by polymerase chain reaction. Results: Mean and peak pulmonary artery pressures assessed by echocardiography were significantiy higher in the DD+ID group compared to the II group (15.2 ±1.6 versus 8.8 ± 0.8 mm Hg, p < 0.01; 32.9 ± 2.5 versus 21.6 ± 2.3 mm Hg, p < 0.05, respectively). The I/D ACE gene polymorphism and FEVl were the only independent predictors of pulmonary artery pressures in multiple linear regression analysis. Conclusion: Our preliminary data indicate that the l/D ACE gene polymorphism is linked to the risk of development of pulmonary hypertension in patients with COPD. Further studies in large groups of patients with COPD are needed to shed more light on this issue.
