A study of the average effect of the 3'APOB-VNTR polymorphism on lipidemic parameters could explain why the short alleles (<35 repeats) are rare in centenarians

BACKGROUND: In studies on the genetics of human aging, we observed an age-related variation of the 3'APOB-VNTR genotypic pool (alleles: Short, S, <35 repeats; Medium, M, 35–39 repeats; Long, L, >39 repeats) with the homozygous SS genotype showing a convex frequency trajectory in a healthy aging population. This genotype was rare in centenarians, thus indicating that the S alleles are unfavorable to longevity, while common in adults, thus indicating a protective role at middle age. This apparent paradox could be due to possible effects exerted by the above polymorphism on lipidemic parameters. Aim of the work was to get insights into these puzzling findings METHODS: We followed a double strategy. Firstly, we analyzed the average effects of S (α(S)), M (α(M)), and L (α(L)) alleles on lipidemic parameters in a sample of healthy people (409 subjects aged 20–102 years) recruited in Calabria (southern Italy). The (α(S)), (α(M)), and (α(L)) values were estimated by relating 3'APOB-VNTR genotypes to lipidemic parameters, after adjustment for age, sex and body mass index (multiple regression). Then, we analyzed the S alleles as susceptibility factors of Cardiovascular Atherosclerotic Disease (CD) in CD patients characterized either by low serum HDL-Cholesterol or by high serum LDL-Cholesterol (CD-H and CD-L patients, 40 and 40 subjects respectively). The Odds Ratios (OR) were computed for carriers of S alleles in CD-H and CD-L patients matched for origin, sex and age with controls extracted from the sample of healthy subjects. RESULTS: By the analysis of the healthy sample group we found that the S alleles lower the average values of serum Total Cholesterol (α(S )= -5.98 mg/dL with [-11.62 ÷ -0.74] 95% confidence interval) and LDL-Cholesterol (α(S )= -4.41 mg/dL with [-8.93 ÷ -0.20] 95% confidence interval) while the alleles M and L have no significant effect on the lipidemic phenotype. In line with these findings, the analysis of CD patients showed that the S alleles are protective as for CD-L (O.R. = 0.55 with [0.21 ÷ 0.98] 95% confidence interval) while neutral as for CD-H (O.R. = 0.75 with [0.32 ÷ 1.60] 95% confidence interval). CONCLUSION: On the whole, the S alleles would be advantageous in adults (by protecting from CD-L) while dangerous in the elderly, probably by lowering serum cholesterol below a critical threshold. This could explain the convex frequency trajectory of SS genotypes previously observed in a healthy aging population

Effect of the 3'APOB-VNTR polymorphism on the lipid profiles in the Guangxi Hei Yi Zhuang and Han populations

<p>Abstract</p> <p>Background</p> <p>Apolipoprotein (Apo) B is the major component of low-density lipoprotein (LDL), very low-density lipoprotein (VLDL) and chylomicrons. Many genetic polymorphisms of the Apo B have been described, associated with variation of lipid levels. However, very few studies have evaluated the effect of the variable number of tandem repeats region 3' of the Apo B gene (3'APOB-VNTR) polymorphism on the lipid profiles in the special minority subgroups in China. Thus, the present study was undertaken to study the effect of the 3'APOB-VNTR polymorphism on the serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations.</p> <p>Methods</p> <p>A total of 548 people of Hei Yi Zhuang were surveyed by a stratified randomized cluster sampling. The epidemiological survey was performed using internationally standardized methods. Serum lipid and apolipoprotein levels were measured. The 3'APOB-VNTR alleles were determined by polymerase chain reaction (PCR) followed by electrophoresis in polyacrylamide gels, and classified according to the number of repeats of a 15-bp hypervariable elements (HVE). The sequence of the most common allele was determined using the PCR and direct sequencing. The possible association between alleles of the 3'APOB-VNTR and lipid variables was examined. The results were compared with those in 496 people of Han who also live in that district.</p> <p>Results</p> <p>Nineteen alleles ranging from 24 to 64 repeats were detected in both Hei Yi Zhuang and Han. HVE56 and HVE58 were not be detected in Hei Yi Zhuang whereas HVE48 and HVE62 were totally absent in Han. The frequencies of HVE26, HVE30, HVE46, heterozygote, and short alleles (< 38 repeats) were higher in Hei Yi Zhuang than in Han. But the frequencies of HVE34, HVE38, HVE40, homozygote, and long alleles (≥ 38 repeats) were lower in Hei Yi Zhuang than in Han (<it>P </it>< 0.05–0.01). The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and Apo B in Hei Yi Zhuang but not in Han were higher in VNTR-LS (carrier of one long and one short alleles) than in VNTR-LL (the individual carrying two long alleles) genotypes. The levels of TC, triglycerides (TG), LDL cholesterol, and Apo B in Hei Yi Zhuang were higher in both HVE34 and HVE36 alleles than in HVE32 allele. The levels of TC, TG, HDL-C and Apo B in Hei Yi Zhuang were also higher in homozygotes than in heterozygotes. There were no significant differences in the detected lipid parameters between the VNTR-SS (carrier of two short alleles) and VNTR-LS or VNTR-LL genotypes in both ethnic groups.</p> <p>Conclusion</p> <p>There were significant differences of the 3'APOB-VNTR polymorphism between the Hei Yi Zhuang and Han populations. An association between the 3'APOB-VNTR polymorphism and serum lipid levels was observed in the Hei Yi Zhuang but not in the Han populations.</p

Association of ACE I/D and MMP-3 5A/6A gene polymorphisms with hypertension in men from Serbia

The ACE and MMP-3 loci are involved in the vascular remodeling, increased intima media thickness and arterial stiffness associated with hypertension. We determined ACE I/D and MMP-3 5A/6A gene polymorphisms in 231 Caucasian males (126/105, hypertensive/normotensive). Owing to age-related differences hypertension, the sample was truncated with respect to age (the cut-off point was the age of 40). Our results indicate that ACE I/D and MMP-3 5A/6A polymorphisms are likely to be risk factors for hypertension in men from Serbia = 40 years of age. In the same group, the combined effect of DD/6A+ genotypes on hypertension was more pronounced than their separate effect.ACE и MMP-3 су укључени у процесе ремоделовања зида крвних судова, задебљања интима-медије и губитка еластичности артерија који су повезани са хипертензијом. Утврђивање генотипова полиморфизама I/D и 5A/6A у генима за ACE и MMP-3 је урађено на узорку од 231 мушкарца, Кавказоида (126/105, хипертензивни/нормотензивни). Обзиром на повезаност настанка хипертензије са годинама старости испитивана популација је подељена у две старосне групе (до и преко 40-е године старости). Наши резултати указују да су полиморфизми у генима за ACE (I/D) и MMP-3 (5A/6A) могући фактори ризика за настанак хипертензије код мушкараца = 40 година старости у популацији Србије. У истој старосној групи заједнички утицај генотипова DD/6A+ на настанак хипертензије је био већи од њиховог појединачног утицаја

Lack of association between eNOS Glu298Asp gene polymorphism and carotid atherosclerosis in a Serbian population.

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The Ala/Ala genotype of PPARY Pro12 Ala polymorphism is associated with late onset of multiple sclerosis

The function of peroxisome proliferator-activated receptor gamma (PPAR gamma) in immune regulation, as well as in anti-inflammatory and anti-proliferative actions towards T lymphocytes, has been reported. A potential role of PPARs in multiple sclerosis (MS) was suggested. The aim of this study was to investigate if there is an association of PPAR gamma-2 Pro12Ala polymorphism with MS in 361 patients from Serbia. The genotype and allele frequencies of Pro12Ala polymorphism were not significantly different between controls and patients, or between females and males. In contrast to controls, we detected a rare Ala/Ala genotype in patients with MS. We found that there is a significant association of Ala/Ala genotype with older age at onset (ANOVA, p=0.07; LSD post-hoc, Ala/Ala vs. Pro/Ala, p=0.03, Ala/Ala vs. Pro/Pro p=0.02). It would be useful to validate our results in other populations, as well as to perform follow-up of the disease progression in regard to PPAR gamma genotypes

Pro12Ala gene polymorphism in the peroxisome proliferator-activated receptor gamma as a risk factor for the onset of type 2 diabetes mellitus in the Serbian population

The peroxisome proliferator-activated receptor gamma (PPAR gamma) is a gene candidate for the onset of type 2 diabetes mellitus (T2DM). We investigated the association of the PPAR gamma Pro12Ala gene with the onset of T2DM for the first time in the Serbian population. The study population consisted of 197 controls and 163 T2DM patients. The 12Ala allele tended to be more frequent in the group of T2DM patients (0.11) compared to the control subjects (0.09). The results from this study indicate that the PPAR gamma(2) 12Ala allele presents a non-significant risk factor for T2DM development in the Serbian population

Spatial variability of indoor radon concentration in schools: implications on radon measurement protocols

The requirements about radon measurements in schools and public buildings included in most of the national and international legislations are generally restricted to certain areas (i.e., radon priority areas) and/or to all the occupied rooms located at ground floor and basement, assuming the soil beneath the building as the main source of indoor radon. In order to assess the quality of such assumption, a study was performed in the framework of a radon survey carried out in 82 buildings (mostly schools and kindergartens) located in 15 Municipalities of Republic of Srpska. Annual radon concentrations have been measured in a total of 185 rooms, some of them (45) located at first floor. In order to minimize the uncertainties due to seasonal variations, the measurement period for radon devices was of one year. Preliminary results of this study show that in 25% of buildings with more than one floor monitored, average radon concentration was higher at first floor than at ground floor. As expected, variability among rooms at the same floor is higher at ground-floor (median CV=22%) than at first floor (median CV=14%). Even if most of the rooms exceeding 300 Bq m–3(the maximum reference level established by 2013/59/Euratom Directive) were located at ground floor (30 out of 32), in one building an exceedance was found at first floor only. These results, if confirmed by further studies, would suggest including in measurement protocols also requirements for rooms located at upper floors: in fact, in some multi-storey buildings, the stack effect and the contribution of building materials may lead to high radon levels also (and sometimes only) at floors not in direct contact with the soil

Y-chromosomal diversity within Europe is clinal and influenced primarily by geography rather than language.

Clinal patterns of autosomal genetic diversity within Europe have been interpreted in previous studies in terms of a Neolithic demic diffusion model for the spread of agriculture; in contrast, studies using mtDNA have traced many founding lineages to the Paleolithic and have not shown strongly clinal variation. We have used 11 human Ychromosomal biallelic polymorphisms, defining 10 haplogroups, to analyze a sample of 3,616 Y chromosomes belonging to 47 European and circum-European populations. Patterns of geographic differentiation are highly nonrandom, and, when they are assessed using spatial autocorrelation analysis, they show significant clines for five of six haplogroups analyzed. Clines for two haplogroups, representing 45% of the chromosomes, are continentwide and consistent with the demic diffusion hypothesis. Clines for three other haplogroups each have different foci and are more regionally restricted and are likely to reflect distinct population movements, including one from north of the Black Sea. Principal-components analysis suggests that populations are related primarily on the basis of geography, rather than on the basis of linguistic affinity. This is confirmed in Mantel tests, which show a strong and highly significant partial correlation between genetics and geography but a low, nonsignificant partial correlation between genetics and language. Genetic-barrier analysis also indicates the primacy of geography in the shaping of patterns of variation. These patterns retain a strong signal of expansion from the Near East but also suggest that the demographic history of Europe has been complex and influenced by other major population movements, as well as by linguistic and geographic heterogeneities and the effects of drift