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Follicle-stimulating hormone receptors (FSHRs) are almost exclusively expressed on granulosa cells, and FSH action is probably most clearly reflected in intrafollicular hormone milieu of antral follicles. Little is known about the possible effects of the common single nucleotide polymorphism (SNP) FSHR -29G > A (rs1394205) on hormonal conditions in humsan small antral follicles (hSAFs) obtained from women in the natural menstrual cycle. This study investigated the follicle fluid (FF) concentrations of anti-Müllerian hormone, estradiol, progesterone, androstenedione, and testosterone in hSAF in relation to the different genotypes of FSHR -29G > A. FF from 362 follicles was collected in 95 women undergoing fertility preservation, who did not suffer from a disease that directly affected ovarian function. The testosterone levels of the minor A/A genotype were significantly increased compared to the A/G and the G/G genotype. Furthermore, significantly reduced androstenedione levels were observed for the G/G genotype, as compared to the A/G genotype, while the other hormones did not show statistical significant differences. In conclusion, the androgen levels of hSAF were significantly elevated in the minor SNP genotype in the FSHR promoter polymorphism FSHR -29G > A. [ABSTRACT FROM AUTHOR]

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Analyzes the relation of human aging with the functional variant of klotho. Reduction on the secreted levels of Klotho harboring V352; Effect of F289V substitution on the ability of F289V to cleave; Influence of KL-VS allele on the trafficking and catalytic activity of Klotho.

We report a large genomic deletion of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, viz., a deletion that is frequently observed in Central and Eastern Europe. The mutation, termed CFTRdele2,3(21 kb), deletes 21,080 bp spanning introns 1–3 of the CFTR gene. Transcript analyses have revealed that this deletion results in the loss of exons 2 and 3 in epithelial CFTR mRNA, thereby producing a premature termination signal within exon 4. In order to develop a simple polymerase chain reaction assay for this allele, we defined the end-points of the deletion at the DNA sequence level. We next screened for this mutation in a representative set of European and European-derived populations. Some 197 CF patients, including seven homozygotes, bearing this mutation have been identified during the course of our study. Clinical evaluation of CFTRdele2,3(21 kb) homozygotes and a comparison of compound heterozygotes for ΔF508/CFTRdele2,3(21 kb) with pairwise-matched ΔF508 homozygotes indicate that this deletion represents a severe mutation associated with pancreatic insufficiency and early age at diagnosis. Current data show that the mutation is particularly common in Czech (6.4% of all CF chromosomes), Russian (5.2%), Belorussian (3.3%), Austrian (2.6%), German (1.5%), Polish (1.5%), Slovenian (1.5%), Ukrainian (1.2%), and Slovak patients (1.1%). It has also been found in Lithuania, Latvia, Macedonia and Greece and has sporadically been observed in Canada, USA, France, Spain, Turkey, and UK, but not in CF patients from Bulgaria, Croatia, Romania or Serbia. Haplotype analysis has identified the same extragenic CF-haplotype XV-2c/KM.19 "A" and the same infrequent intragenic microsatellite haplotype 16–33–13 (IVS8CA-IVS17bTA-IVS17bCA) in all examined CFTRdele2,3(21 kb) chromosomes, suggesting a common origin for this deletion. We conclude that the 21-kb deletion is a frequent and severe CF mutation in populations of Eastern- and Western-Slavic descent. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) patients show a high degree of linkage disequilibrium between the CF transmembrane conductance regulator ( CFTR) gene and polymorphisms 5′ of that gene. To determine whether the region 5′ of CFTR contains biologically important sequences, the allele frequencies of six CFTR-linked polymorphisms (metH/ MspI, XV-2c/ TaqI, CS.7/ HhaI, KM19/ PstI, MP6-d9/ MspI, J44/ XbaI) were determined in 417 randomly selected elderly individuals (over 75 years of age) from the Czech population. The elderly individuals were considered “escapees” of strong selective pressures that had operated during their lifetime, prior to the introduction of modern health care since 1950. The pooled allele frequencies of the analyzed marker polymorphisms in the elderly did not significantly differ from published data. However, when analyzed by sex, the allele frequencies of markers CS.7/ HhaI and KM19/ PstI differed significantly ( P < 0.05) between elderly females and males. The allele frequencies of the six polymorphisms were then determined in 646 newborns and 345 young adults of reproductive age; these individuals were selected in a similar manner and drawn from the same population. In these control groups, the studied marker polymorphisms exhibited no statistically significant differences between sexes and/or between individuals of the same sex, only between different age groups. A gradual relative increase in the frequency of allele “2” of marker CS.7/ HhaI was observed from newborn females to elderly women, the overall difference in allele frequencies of this marker polymorphism between newborn females and elderly women reaching statistical significance ( P < 0.05). Interestingly, allele “2” is the major constituent of the extended “B-haplotype”, which is in strong linkage disequilibrium with common CF alleles. Taken together, our data suggest that the region spanning markers CS.7 and KM19 is associated with a genetic factor that influences postnatal female survival, providing a possible mechanism for increasing the frequency of particular mutations in the adjacent CFTR gene. [ABSTRACT FROM AUTHOR]

Cílem práce bylo vypracování metodického postupu laboratorního, ultrazvukového a klilnicko-genetického vyšetření k časnému záchytu gravidit se zvýšeným rizikem preeklampsie (PE) pro prevenci a léčbu anopyrinem mezi 13.-16. týdnem gravidity. Hladiny PAPP-A a PIGF byly stanoveny na systému Kryptor (Brahms) a Delfia Xpress (Perkin Elmer). Riziko PE bylo určeno softwarem Preeclampsia Predictor (Perkin Elmer) hodnotícím klinicko-anamnestické údaje, hladiny PAPP-A a PIGF, střední arteriální tlak a pulzatilitu aa. uterinae. Tento software je použitelný pouze pro rizika v I. trimestru. Riziko je zvýšené, pokud je vyšší než 1:20. Kontrolní hladiny PIGF v naší populaci byly stanoveny z 800 vzorků v rozmezí 9.-19. týdne gravidity. Hladiny menší než 3. a 5. percentil jsou hodnoceny jako významně snížené v I. a II. trimestru. Kontrolní hladiny odpovídají přesně evropským normám (Perkin Elmer), tak jako jejich lineární růst v I. a II. trimestru. Naše studie prokázala, že klinická závažnost a časnost nástupu PE je nepřímo úměrná hladinám PIGF. Medián PIGF (PE 24.-29. týden) je 29,9 pg/ml, pro PE v 30.-33. týdnu je 54,9 pg/ml, v 34.-41. týdnu je v rozmezí 76,6-80,1 pg/ml. Pro určení rizika PE po 20. týdnu gravidity je významné naše zjištění, že u nejtěžších PE (24.-29. týden) hladina PIGF nepřevýší kontrolní hladiny pro 75. percentil, odpovídající 14. týdnu. U PE v 30.-33. týdnu nepřesahují 14. týden, v týdnu 34.-41. pro 20. týden. Výsledky screeningu prvních 50 rizikových gravidit zachytily 2 ženy se zvýšeným rizikem časné a 6 žen s rizikem pozdní PE. Výsledky nasvědčují, že s nejvyšším rizikem PE je spojena PE v předchozích graviditách a hypertenze, kombinovaná s dalšími klinickými rizikovými faktory. Získané výsledky umožňují rozvinout screening PE nejenom u rizikových gravidit, ale jsou také součástí screeningu v I. trimestru ke zvýšení jeho efektivity i v záchytu aneuploidií. [ABSTRACT FROM AUTHOR]