The development of surface measurements of the palpebral fissures and age-related changes in the quality of the relationships between the individual measurements were followed in 1552 healthy Caucasians between ages 2 and 18. At age 2, the height of the palpebral fissure and the biocular width (ex-ex) were the most developed features (93.3% and 86%) and the least developed was the intercanthal width (77.6% to 82.9%). The measurements reached adult size between ages 8 (intercanthal width in girls) and 16 (palpebral fissure inclination in boys). The rate of growth in the orbital measurements was usually moderate, seldom above-average and fast only in intercanthal width between ages 3 and 4. The study determined the periods with minimal growth (approximately ages 5 to 7 and 9 to 10) for each of the measurements. After maturation, the changes in measurements were minimal. A knowledge of the developmental levels of the measurements at an early age, their changes with age and their maturation times are of great importance in timing early or final corrective surgical procedures.

• MeSH
• běloši * MeSH
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• orbita anatomie a histologie   růst a vývoj   MeSH
• předškolní dítě MeSH
• referenční hodnoty MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Idiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies. METHODS: We collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups. RESULTS: We report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10-5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10-53 and HLA-DRB1*03:01, p=3.25×10-9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10-26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10-11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10-13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10-6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10-64) and position 9 of HLA-B (p=7.03×10-11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies. CONCLUSIONS: These findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.

• Klíčová slova
• HLA, autoantibody, genetics, idiopathic inflammatory myopathy, myositis,
• MeSH
• alely MeSH
• autoprotilátky genetika   imunologie   MeSH
• běloši genetika   MeSH
• dospělí MeSH
• genotyp MeSH
• haplotypy MeSH
• HLA-DRB1 řetězec genetika   imunologie   MeSH
• hlavní histokompatibilní komplex genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida genetika   imunologie   MeSH
• polymorfismus genetický MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• HLA-DRB1 řetězec MeSH

The FTO gene variants are the most important genetic determinants of body weight and obesity known so far, but the mechanism of their effect remains unclear. We have analyzed FTO rs17817449 variant (G>T in first intron) in 6024 adults aged 45-69 years to assess the potential mediating role of diet and physical activity. Diet was assessed by a 140-item food frequency questionnaire. Physical activity was measured by hours spent during a typical week by sport, walking and other activities outside of work requiring heavy and medium physical activity. Basal metabolic rate was calculated according Schofield formula. The FTO variant was significantly associated with body mass index (means in GG, GT and TT carriers were 28.7, 28.2 and 27.8 kg/m(2), p<0.001) and basal metabolic rate (BMR) (means in GG, GT and TT were 1603, 1588 and 1576 kcal per day, respectively, p<0.008) but it was not associated with physical activity, total energy intake or with energy intakes from fat, carbohydrates, proteins or alcohol. Results were essentially similar in men and women and the adjustment for physical activity or dietary energy intake did not reduce the effect of the FTO polymorphism. Means of BMR per kg of body weight was lowest in GG carriers (20.09, 20.21 for GT and 20.30 for TT, p<0.006) and this effect was more pronounced in females. These results suggest that the effect of the FTO rs17817449 variant on BMI in Caucasian adults is not mediated by energy intake or physical activity, but some effect on BMR per kg of body weight is possible.

• MeSH
• bazální metabolismus genetika   MeSH
• běloši genetika   MeSH
• cvičení * MeSH
• energetický příjem genetika   MeSH
• gen pro FTO MeSH
• index tělesné hmotnosti MeSH
• jednonukleotidový polymorfismus * MeSH
• lidé středního věku MeSH
• lidé MeSH
• proteiny genetika   MeSH
• složení těla genetika   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• FTO protein, human MeSH Prohlížeč
• gen pro FTO MeSH
• proteiny MeSH

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of type 2 diabetes mellitus (T2DM). Several lines of evidence implicate the endothelin (ET) system in the pathophysiology of DN. The aim of the present study was to analyze if genetic polymorphisms of the ET-1 (EDN1) gene affect susceptibility to DN in Caucasians with T2DM. MATERIALS AND METHODS: The study population consisted of 651 Caucasian subjects with T2DM of more than 10 years' duration: 276 patients with DN (cases) and 375 patients without evidence of DN (controls). Polymorphisms in ET-1 (EDN1) gene, rs5370, rs1476046, and rs3087459, were studied. RESULTS: Genotype distributions of the studied polymorphisms showed no significant difference between cases and controls. CONCLUSIONS: We provide evidence that the rs5370, rs1476046, and rs3087459 polymorphisms of EDN1 gene are not risk factors for DN in Caucasians with T2DM.

• Klíčová slova
• diabetic nephropathy, endothelin-1 gene polymorphisms, type 2 diabetes mellitus,
• MeSH
• běloši genetika   MeSH
• diabetes mellitus 2. typu etnologie   genetika   patofyziologie   MeSH
• diabetické nefropatie etnologie   genetika   patofyziologie   MeSH
• dospělí MeSH
• endotelin-1 genetika   MeSH
• genetická predispozice k nemoci epidemiologie   MeSH
• hodnocení rizik MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• průřezové studie MeSH
• referenční hodnoty MeSH
• retrospektivní studie MeSH
• senzitivita a specificita MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• endotelin-1 MeSH

In order to investigate the contribution of candidate genes in the RAAS in pathogenesis of EAH, we analysed the M235T polymorphism of the angiotensinogen gene, and the I/D polymorphism of ACE gene in a group of adult Caucasians (Slovene population) with EAH. Four-hundred and thirteen unrelated subjects with the diagnosis of EAH were included in the association study and they were compared to 414 subjects with normal blood pressure (the control group). The M235T angiotensinogen genotype distribution in patients with EAH (TT = 23.2%, MT = 48.7%, MM = 28.1%) did not differ from genotype distribution in controls (TT = 21.1%, MT = 49.0%, MM = 29.9%), and the TT genotype was not associated with EAH (OR 1.1; 95% CI 0.7-1.7; P = 0.6). Moreover, The I/D ACE genotype distribution in patients with EAH (DD = 32.0%, ID = 48.2%, II = 19.8%) did not differ from genotype distribution in controls (DD = 32.2%, ID = 49.0%, II = 18.8%), and the DD genotype was not associated with EAH (OR 1.0; 95% CI 0.7-1.3; P = 0.9). In conclusion, we failed to demonstrate that the M235T angiotensinogen polymorphism and the ACE I/D polymorphism were genetic markers for EAH in adult Caucasians.

• MeSH
• angiotensin konvertující enzym genetika   MeSH
• angiotensinogen genetika   MeSH
• běloši genetika   MeSH
• genotyp MeSH
• hypertenze genetika   MeSH
• lidé MeSH
• methionin genetika   MeSH
• polymorfismus genetický genetika   MeSH
• studie případů a kontrol MeSH
• threonin genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ACE protein, human MeSH Prohlížeč
• angiotensin konvertující enzym MeSH
• angiotensinogen MeSH
• methionin MeSH
• threonin MeSH

BACKGROUND: Several genetic polymorphisms influence the risk of heavy alcohol consumption but it is not well understood whether the genetic effects are similar in different populations and drinking cultures, nor whether the genetic influences on binge drinking are similar to those seen for alcoholism. METHODS: We have analyzed the effect of the Arg47His (rs1229984) variant within the alcohol dehydrogenase (ADH1B) gene on a range of drinking related variables in a large Eastern European Slavic population (Czech HAPIEE study), which recruited random samples of men and women aged 45-69 years in 7 Czech towns (3,016 males and 3,481 females with complete data). Drinking frequency, annual alcohol intake, prevalence of binge drinking (≥100 g in men and ≥60 g in women at least once a month) and the mean dose of alcohol per occasion were measured by the graduated frequency questionnaire. Alcohol intake in a typical week was used to define heavy drinking (≥350 g/wk in men and ≥210 g in women). Problem drinking (≥2 positive answers on CAGE) and negative consequences of drinking on different aspects of life were also measured. RESULTS: The frequency of the His47 allele carriers was 11%. Homozygotes in the common allele (Arg47Arg), among both males and females, had significantly higher drinking frequency, and annual and weekly intake of alcohol than His47 carriers. The odds ratio of heavy drinking in Arg47Arg homozygotes versus His47 carriers was 2.1 (95% confidence intervals 1.1-3.2) in men and 2.2 (1.0-4.7) in women. In females, but not in males, Arg47Arg homozygotes had marginally significantly higher prevalence of binge drinking and mean alcohol dose per drinking session. There was no consistent association with problem drinking and negative consequences of drinking. CONCLUSIONS: The ADH1B genotype was associated with the frequency and volume of drinking but its associations with binge drinking and problem drinking were less consistent.

• MeSH
• alkoholdehydrogenasa genetika   MeSH
• běloši MeSH
• lidé středního věku MeSH
• lidé MeSH
• missense mutace MeSH
• pití alkoholu genetika   MeSH
• polymorfismus genetický * MeSH
• poruchy způsobené alkoholem genetika   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• ADH1B protein, human MeSH Prohlížeč
• alkoholdehydrogenasa MeSH

Iron metabolism might be involved in the pathogenesis of CAD, and C282Y and H63D mutations in the HFE gene are associated with increased serum iron levels and net iron accumulation. The aim of this study was to look for a relationship between the C282Y and H63D gene mutations of the HFE gene and coronary artery disease (CAD) in a group of patients with type 2 diabetes lasting more than 10 years. The C282Y and H63D gene mutations were tested in 338 Caucasians with type 2 diabetes: 156 cases with CAD and 182 subjects with no history of CAD. The C282Y and the H63D HFE gene distributions in patients with CAD (C282Y: YY 0.6%, CY 9.0%, CC 90.4%; H63D: DD 3.8%, HD 21.8%, HH 74.4%) were not significantly different from those of diabetic subjects without CAD (C282Y: YY 0%, CY 8.2%, CC 91.8%; H63D: DD 2.2%, HD 20.3%, HH 77.5%). In conclusion, we failed to demonstrate that the C282Y and H63D HFE gene mutations were risk factors for CAD in Caucasians with type 2 diabetes lasting longer than 10 years.

• MeSH
• diabetes mellitus 2. typu komplikace   genetika   MeSH
• genetická vazba * MeSH
• hemochromatóza komplikace   genetika   MeSH
• lidé MeSH
• mutace genetika   MeSH
• nemoci koronárních tepen etiologie   genetika   MeSH
• rizikové faktory MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• železo MeSH

The PGC-1 gene has been implicated in the regulation of several genes controlling energy metabolism. The prevalent Gly482Ser polymorphism of the PGC-1 gene has been shown to be associated with type 2 diabetes in some but not all studies. The aim of this study was to analyse whether the Gly482Ser variant is a risk factor for development of type 2 diabetes in Slovene population (Caucasians). Genotyping of the Gly482Ser polymorphism was performed for 545 subjects: 305 patients with type 2 diabetes and 240 non-diabetic controls. The Gly482Ser genotype distribution in patients with type 2 diabetes (AA = 11.5%, AG = 42.3%, GG = 46.2%) differed from genotype distribution in non-diabetic controls (AA = 6.3%, AG = 46.3%, GG = 47.5%), and the AA genotype was associated with 1.9-times increased risk of type 2 diabetes (95% confidence interval 1.0-3.6; P = 0.036). In conclusion, we suggest that the AA genotype of the Gly482Ser polymorphism of the PGC-1 gene should be considered as a risk factor for the development of type 2 diabetes in Caucasians.

• MeSH
• běloši genetika   MeSH
• diabetes mellitus 2. typu etnologie   genetika   MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci * MeSH
• glycin genetika   MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• rizikové faktory MeSH
• serin genetika   MeSH
• studie případů a kontrol MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Slovinsko MeSH
• Názvy látek
• glycin MeSH
• peroxisome-proliferator-activated receptor-gamma coactivator-1 MeSH Prohlížeč
• serin MeSH
• transkripční faktory MeSH

Gender differences in CAD have been clearly documented, and sex hormones have been recognized to influence the risk of CAD. The cytochrome P450c17alpha gene (CYP17) and the CYP19 gene influence concentrations of sex hormones. In this cross-sectional association study we tested the hypothesis whether the T/C polymorphism of the CYP17 gene and the tetranucleotide repeat (TTTA) polymorphism of the CYP19 gene are genetic markers for CAD in Caucasians. The TT genotype of the CYP17 gene polymorphism was not associated with premature CAD in men and women combined (OR 0.9; 95% CI = 0.6-1.4; P = 0.7), in men only (OR 1; 95% CI = 0.6-1.8; P = 0.7), and in women only (OR 0.8; 95% CI = 0.5-1.4; P = 0.4). The tetranucleotide repeat (TTTA) CYP19 gene polymorphism was not associated with premature CAD. Moreover, the genotypes containing the longer alleles (A6 or A7) were not associated with a lower incidence of CAD, and the genotypes containing the shorter alleles (A1 or A2) were not over-represented in the CAD patients. We may conclude that in Caucasian subjects neither the T/C CYP17 gene polymorphism nor the tetranucleotide repeat (TTTA) polymorphism of the CYP19 gene contributes to the genetic susceptibility to CAD, therefore they may not be used as genetic markers for CAD risk assessment.

• MeSH
• alely MeSH
• aromatasa genetika   MeSH
• běloši genetika   MeSH
• genetické markery genetika   MeSH
• genotyp MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrosatelitní repetice genetika   MeSH
• nemoci koronárních tepen etnologie   genetika   MeSH
• polymorfismus genetický * MeSH
• steroid-17-alfa-hydroxylasa genetika   MeSH
• studie případů a kontrol MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aromatasa MeSH
• genetické markery MeSH
• steroid-17-alfa-hydroxylasa MeSH

The INSIG2 (INSIG2 is primarily involved in the regulation of fatty acid and cholesterol synthesis) gene is suggested to be obesity related. An INSIG2 promoter variant, G-102A, has been detected and was demonstrated to be of potential functional significance. In two cohorts of middle-aged men, the association between this variant and BMI was suggested. We sought to replicate the association between the INSIG2 G-102A variant and BMI in three large Slavonic Caucasian populations. Further, we analysed the possible effect of this variant on BMI changes in a short-time intervention study. One thousand ninety-nine males and 1368 females (population- based Czech MONICA three-year cohort), 908 females from the 3PMFs study, together with 94 overweight (BMI > 27 kg/m2) females who underwent nine weeks of dietary/exercise intervention were genotyped for the INSIG2 G-102A variant using PCR-RFLP analysis. We could not detect any association between the INSIG2 G-102A variant and BMI or WHR with or without adjusting for age and gender in any population. Neither the BMI change nor anthropometric and lipid parameter changes were affected by the INSIG2 G-102A gene variant in intervened overweight females. However, MONICA females (but not males) carrying the common GG genotype had higher plasma levels of HDL cholesterol (GG homozygotes 1.51 ± 0.36 mmol/l vs. A allele carriers 1.45 ± 0.33; P < 0.05) in both surveys. Our results indicated that the G-102A INSIG2 polymorphism has no consistent effect on BMI in general populations, but could influence HDL cholesterol in females.

• MeSH
• alely MeSH
• běloši MeSH
• dospělí MeSH
• frekvence genu genetika   MeSH
• genetická predispozice k nemoci MeSH
• HDL-cholesterol genetika   MeSH
• index tělesné hmotnosti MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• promotorové oblasti (genetika) 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
• Názvy látek
• HDL-cholesterol MeSH
• INSIG2 protein, human MeSH Prohlížeč
• intracelulární signální peptidy a proteiny MeSH
• membránové proteiny MeSH