Longevity is a hallmark of successful ageing and a complex trait with a significant genetic component. In this study, 43 single nucleotide polymorphisms (SNPs) were chosen from the literature and ...genotyped in a Croatian oldest-old sample (85+ years, sample size (N) = 314), in order to determine whether any of these SNPs have a significant effect on reaching the age thresholds for longevity (90+ years, N = 212) and extreme longevity (95+ years, N = 84). The best models were selected for both survival ages using multivariate logistic regression. In the model for reaching age 90, nine SNPs explained 20% of variance for survival to that age, while the 95-year model included five SNPs accounting for 9.3% of variance. The two SNPs that showed the most significant association (p ≤ 0.01) with longevity were TERC rs16847897 and GHRHR rs2267723. Unweighted and weighted Genetic Longevity Scores (uGLS and wGLS) were calculated and their predictive power was tested. All four scores showed significant correlation with age at death (p ≤ 0.01). They also passed the ROC curve test with at least 50% predictive ability, but wGLS90 stood out as the most accurate score, with a 69% chance of accurately predicting survival to the age of 90.
The products of the polymorphic ADME genes are involved in Absorption, Distribution, Metabolism, and Excretion of drugs. The pharmacogenetic data have been studied extensively due to their clinical ...importance in the appropriate drug prescription, but such data from the isolated populations are rather scarce. We analyzed the distribution of 95 polymorphisms in 31 core ADME genes in 20 populations worldwide and in newly genotyped samples from the Roma (Gypsy) population living in Croatia. Global distribution of ADME core gene loci differentiated three major clusters; (1) African, (2) East Asian, and (3) joint European, South Asian and South American cluster. The SLCO1B3 (rs4149117) and CYP3A4 (rs2242480) genes differentiated at the highest level the African group of populations, while NAT2 gene loci (rs1208, rs1801280, and rs1799929) and VKORC1 (rs9923231) differentiated East Asian populations. The VKORC1 rs9923231 was among the investigated loci the one with the largest global minor allele frequency (MAF) range; its MAF ranged from 0.027 in Nigeria to 0.924 in Han Chinese. The distribution of the investigated gene loci positions Roma population within the joined European and South Asian clusters, suggesting that their ADME gene pool is a combination of ancestral (Indian) and more recent (European) surrounding, as it was already implied by other genetic markers. However, when compared to the populations worldwide, the Croatian Roma have extreme MAF values in 10 out of the 95 investigated ADME core gene loci. Among loci which have extraordinary MAFs in Roma population two have strong proof of clinical importance: rs1799853 (CYP2C9) for warfarin dosage, and rs12248560 (CYP2C19) for clopidogrel dosage, efficacy and toxicity. This finding confirms the importance of taking the Roma as well as the other isolated populations`genetic profiles into account in pharmaco-therapeutic practice.
Estimating individual genome-wide autozygosity is important both in the identification of recessive disease variants via homozygosity mapping and in the investigation of the effects of genome-wide ...homozygosity on traits of biomedical importance. Approaches have tended to involve either single-point estimates or rather complex multipoint methods of inferring individual autozygosity, all on the basis of limited marker data. Now, with the availability of high-density genome scans, a multipoint, observational method of estimating individual autozygosity is possible. Using data from a 300,000 SNP panel in 2618 individuals from two isolated and two more-cosmopolitan populations of European origin, we explore the potential of estimating individual autozygosity from data on runs of homozygosity (ROHs). Termed F
roh, this is defined as the proportion of the autosomal genome in runs of homozygosity above a specified length. Mean F
roh distinguishes clearly between subpopulations classified in terms of grandparental endogamy and population size. With the use of good pedigree data for one of the populations (Orkney), F
roh was found to correlate strongly with the inbreeding coefficient estimated from pedigrees (r = 0.86). Using pedigrees to identify individuals with no shared maternal and paternal ancestors in five, and probably at least ten, generations, we show that ROHs measuring up to 4 Mb are common in demonstrably outbred individuals. Given the stochastic variation in ROH number, length, and location and the fact that ROHs are important whether ancient or recent in origin, approaches such as this will provide a more useful description of genomic autozygosity than has hitherto been possible.
The Roma population suffers from severe poverty, social exclusion, and some of the worst health conditions in the industrialized world. Herein, we report on cardiovascular disease (CVD) risk factors ...in the Ukrainian Roma and present a meta-analysis of the prevalence of CVD risk factors in 16 Roma populations worldwide. The meta-analyses of CVD risk factors in Roma (n = 16,552) vs. non-Roma majority population of the same country (n = 127,874) included publicly available data. Ukrainian field survey included 339 adults of both sexes and outcomes of interest were hypertension, body mass index (BMI), smoking, education, and employment status. Furthermore, 35.7% of the Ukrainian Roma were hypertensive, 69.3% unemployed, and 48.4% never went to school. Ukrainian Roma women were more likely to be underweight and more prone to be hypertensive, with odds of hypertension increasing with age, BMI, and positive smoking status. Meta-analyses showed that, in comparison with non-Roma worldwide, the Roma bear significantly higher risk factor loads related to smoking (OR = 2.850), diabetes (OR = 1.433), abdominal obesity (OR = 1.276), and metabolic syndrome (OR = 1.975), with lower loads for hypertension (OR = 0.607) and BMI ≥ 25 kg/m2 (OR = 0.872). To conclude, the CVD risk factors which are more common in Roma than in the majority population may reflect their poor health-related behaviors and inadequate access to health education.
Aim
To determine to what extent the lifestyle and psychological factors influenced the occurrence of obesity in the population of the Mediterranean island of Vis (Croatia); also to relate the ...examined risk factors to several obesity indicators in order to select the most sensitive one.
Methods
Cross‐sectional population study included 960 participants of both sexes (18–93 years) in whom the obesity was estimated using anthropometric indicators. The factor analysis of 55‐item Food Frequency Questionnaire (FFQ) was performed as well as the General Health Questionnaire (GHQ12) for the self‐assessment of psychological health and wellbeing. FFQ and GHQ12 individual factors’ scores, sex, age, physical activity, smoking and socioeconomic status were further used as independent variables in the multiple linear regression analyses with five obesity indicators as dependent variables.
Results
The examined risk factors explained the highest proportion of variance of the waist to height ratio (WHtR) in comparison with all other indicators of obesity (body mass index (BMI), waist to hip ratio, sum of skinfolds thicknesses, fat mass percentage). Only the dietary factors showed a significant relation to BMI, while almost all of the tested variables–dietary pattern, psychological structure, smoking habit and physical activity–had a significant association with WHtR.
Conclusions
WHtR is the most useful indicator of obesity as it had a profiled relation with a number of lifestyle factors as well as with psychological health. The present study also revealed the importance of psychological factors for obesity phenotype, particularly the behavioural pattern which could be described as avoidance of dealing with problems.
The study was designed as a gerontologic-public health analysis of the relationship between the leading and accompanying psychogeriatric diagnoses and negative health behaviors recorded in the old ...people's home users, with the aim to evaluate and redefine gerontologic-public health priorities and geroprophylactic measures, with special reference to persons suffering from Alzheimer's disease and other dementias.
Gerontologic-public health indicators obtained by monitoring health care needs of the elderly in specific institutional primary health care at 10 old people's homes (N=1185) in Croatia in 2013 were analyzed using the professional methodology developed at Department of Health Gerontology, Andrija Štampar Teaching Institute of Public Health (Registry List 1 that refers to monitoring specific primary health care needs of elderly at old people's homes).
Study results revealed that essential arterial hypertension was the principal (leading) principal diagnosis in the old people's home users as of 2013, accounting for 13% of all leading diagnoses recorded in the elderly in institutional health care. In the study population, psychogeriatric diagnoses were recorded among the first five accompanying and leading diagnoses. Refusal of occupational therapy was the most common unfavorable health behavior recorded in the old people's home users, accounting for 22%, followed by poor personal and environmental hygiene (19%), physical inactivity (18%), mental inactivity (15%), obesity (13%) and smoking (5%) of 861 unfavorable behaviour characteristics recorded in study subjects. Study results showed the leading diagnoses in the old people's home users (such as circulatory system diseases, hip fracture, non-insulin dependent diabetes mellitus) to be associated with negative health behaviors that can be considered as risk factors for the development or progression of the disease, in psychogeriatric patients in particular.
The results obtained by gerontological-public health indicator analysis indicate that programs of geroprophylaxis, gerontologic and psychogeriatric measures should be implemented in old people's homes as a priority, with day centers for Alzheimer's disease patients. It is necessary to identify and evaluate risk factors for the occurrence of preventable diseases, change the negative health behaviors in the elderly, and apply the nutritional-gerontologic dietary standards at old people's homes including follow up of dietary intake of nutrients such as vitamins and mineral, with special reference to psychogeriatric patients.
Multiple studies have provided compelling evidence that the FTO gene variants are associated with obesity measures. The objective of the study was to investigate whether FTO variants are associated ...with a broad range of obesity related anthropometric traits in an island population.
We examined genetic association between 29 FTO SNPs and a comprehensive set of anthropometric traits in 843 unrelated individuals from an island population in the eastern Adriatic coast of Croatia. The traits include 11 anthropometrics (height, weight, waist circumference, hip circumference, bicondilar upper arm width, upper arm circumference, and biceps, triceps, subscapular, suprailiac and abdominal skin-fold thicknesses) and two derived measures (BMI and WHR). Using single locus score tests, 15 common SNPs were found to be significantly associated with "body fatness" measures such as weight, BMI, hip and waist circumferences with P-values ranging from 0.0004 to 0.01. Similar but less significant associations were also observed between these markers and bicondilar upper arm width and upper arm circumference. Most of these significant findings could be explained by a mediating effect of "body fatness". However, one unique association signal between upper arm width and rs16952517 (P-value = 0.00156) could not be explained by this mediating effect. In addition, using a principle component analysis and conditional association tests adjusted for "body fatness", two novel association signals were identified between upper arm circumference and rs11075986 (P-value = 0.00211) and rs16945088 (P-value = 0.00203).
The current study confirmed the association of common variants of FTO gene with "body fatness" measures in an isolated island population. We also observed evidence of pleiotropic effects of FTO gene on fat-free mass, such as frame size and muscle mass assessed by bicondilar upper arm width and upper arm circumference respectively and these pleiotropic effects might be influenced by variants that are different from the ones associated with "body fatness".
To determine variation of CYP2B6 gene within the genetically specific Croatian Roma (Gypsy) population originating from India and to examine it in the worldwide perspective.
Seven SNP loci ...(rs12721655, rs2279343, rs28399499, rs34097093, rs3745274, rs7260329 and rs8192709) were genotyped in 439 subjects using Kompetitive Allele Specific PCR (KASP) method.
The Croatian Roma took an outlying position in CYP2B6 variation from the worldwide perspective mainly due to their exceptionally high minor allele frequency (MAF) for rs8192709 (12.8%), and lower for rs2279343 (21.1%) compared with south Asian populations.
This study provides the first data of several CYP2B6 polymorphisms in Roma population and indicates the need for systematic investigation of the most important pharmacogenes' variants in this large, transnationally isolated population worldwide.
The human angiotensin converting enzyme (ACE) gene is one of the most investigated candidate genes for cardiovascular diseases (CVD), but the understanding of its role among the elderly is vague. ...Therefore, this study focuses at: (a) testing the association of ACE polymorphism with CVD risk factors among the elderly, and (b) detecting the possible unequal distribution of ACE genotypes between senescent and younger segments of the European populations. The association of ACE I/D polymorphism with CVD health status hypertension (HT), obesity, dislypidemia in 301 very old subjects (88.2 ± 5 years; F/M = 221/80) was tested by means of logistic regression analysis. The meta-analysis of D allele frequency in general vs. elderly (80+ years) groups was conducted using all publicly available data for European populations comprising both age cohorts. Multiple multinomial logistic regression revealed that within this elderly sample, age (younger olds, 80–90 years), female sex (OR = 3.13, 95% CI = 1.59–6.19), and elevated triglycerides (OR = 2.53, 95% CI = 1.29–4.95) were positively associated with HT, while ACE polymorphism was not. It was also established that the DD genotype was twice as high in 80+ cohort compared to general population of Croatia (
p
< 0.00001). This trend was confirmed by the meta-analysis that showed higher D allele frequencies in olds from nine of ten considered European populations (OR = 1.19, 95% CI = 1.08–1.31). The data in elderly cohort do not confirm previously reported role of ACE DD genotype to the development of HT. Moreover, meta-analysis indicated that ACE D allele has some selective advantage that contributes to longevity in majority of European populations.
Leptin, a possible mediator between energy homeostasis, inflammation and cardiovascular disease (CVD), acts via leptin receptors. We investigated association of single-nucleotide polymorphisms (SNPs) ...and haplotypes of the leptin receptor gene (LEPR) with several CVD risk factors: body mass index, waist circumference (WC), serum lipids, fibrinogen and C-reactive protein levels. Thirty-one SNPs in and near LEPR gene were analyzed in 986 inhabitants of the island of Vis, Croatia and 29 SNPs in the inland sample (N=499). We assessed linkage disequilibrium (LD), SNP and haplotype associations with the selected phenotypes. rs4291477 significantly associated with fibrinogen (P=0.003) and rs7539471 marginally significantly with high-density lipoprotein (P=0.004), but only in the Vis sample, while rs10493384 marginally significantly associated with triglyceride levels (P=0.006) in the inland sample. SNPs were grouped into eight LD blocks in Vis and in seven blocks in the inland population. Haplotype A-C-A-A-G-A in block 5 in Vis (rs1782754, rs1171269, rs1022981, rs6673324, rs3790426, rs10493380) and haplotype A-A-A-A in block 4 in the inland data (rs1782754, rs1022981, rs6673324, rs1137100) were nominally associated with WC, P=7.085 × 10(-22) (adjusted P=0.0979) and P=5.496 × 10(-144) (adjusted P=0.1062), respectively.
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