Abstract Many polymorphisms have been identified in human mitochondrial DNA by using different techniques. The polymorphisms found have shed light on the history of human populations and on some complex traits.
A genetic perspective of human history in Europe was derived from 22 binary markers of the nonrecombining Y chromosome (NRY). Ten lineages account for >95% of the 1007 European Y chromosomes studied. Geographic distribution and age estimates of alleles are compatible with two Paleolithic and one Neolithic migratory episode that have contributed to the modern European gene pool. A significant correlation between the NRY haplotype data and principal components based on 95 protein markers was observed, indicating the effectiveness of NRY binary polymorphisms in the characterization of human population composition and history.
Centenarians represent a biological model of successful aging because they escaped/postponed most invalidating age-related diseases, such as cardiovascular diseases. The aim of the present study was to clarify whether a favorable cardiovascular risk profile increases the survival chances in long-lived people.A total of 355 community-dwelling nonagenarians and centenarians living in Southern Italy were recruited in the study. Patients were classified as at low and high cardiovascular risk on the basis of serum cholesterol, diabetes, hypertension and smoking status. The relationship between cardiovascular risk factors and 10-year mortality was investigated by Cox regression analysis. Splines-based hazard ratio curves were also estimated for total cholesterol, low-density lipoprotein cholesterol, and systolic and diastolic blood pressure.Low levels of selected cardiovascular risk factors usually associated with lower mortality in adults do not increase survival chances among oldest-old individuals. In particular, after adjusting for age, sex, and cognitive, functional and nutritional status, serum cholesterol >200 mg/dL increased the survival chances during the follow-up period (hazard ratio 0.742, 95% CI 0.572-0.963).The present results showed that in nonagenarians and centenarians, the clinical and prognostic meaning associated with traditional cardiovascular risk factors is very different from younger populations. Consequently, considering the increase of this population segment, further studies are required to confirm these results and to translate them into clinical practice/primary care. Geriatr Gerontol Int 2019; 19: 165-170.
Genetic association studies of age-related, chronic human diseases often suffer from a lack of power to detect modest effects. Here we propose an alternative approach of including healthy centenarians as a more homogeneous and extreme control group. As a proof of principle we focused on type 2 diabetes (T2D) and assessed /genotypic associations of 31 SNPs associated with T2D, diabetes complications and metabolic diseases and SNPs of genes relevant for telomere stability and age-related diseases. We hypothesized that the frequencies of risk variants are inversely correlated with decreasing health and longevity. We performed association analyses comparing diabetic patients and non-diabetic controls followed by association analyses with extreme phenotypic groups (T2D patients with complications and centenarians). Results drew attention to rs7903146 (TCF7L2 gene) that showed a constant increase in the frequencies of risk genotype (TT) from centenarians to diabetic patients who developed macro-complications and the strongest genotypic association was detected when diabetic patients were compared to centenarians (p_value = 9.066*10⁻⁷). We conclude that robust and biologically relevant associations can be obtained when extreme phenotypes, even with a small sample size, are compared.
Abstract Background Chronic kidney disease (CKD) and hypertension are chronic diseases affecting a large portion of the population, frequently coexistent and interdependent. The inability to produce/use adequate renal dopamine may contribute to the development of hypertension and renal dysfunction. The heterodimeric amino acid transporter LAT2/4F2hc (SLC7A8/SLC3A2 genes) promotes the uptake of L-DOPA, the natural precursor of dopamine. We examined the plausibility that SLC7A8/SLC3A2 gene polymorphisms may contribute to hypertensive CKD by affecting the L-DOPA uptake. Methods 421 subjects (203 men and 218 women, mean age of 78.9 ± 9.6 years) were recruited and divided in four groups according to presence/absence of CKD, defined as reduced estimated glomerular filtration rate (eGFR < 60 ml/min/m2) calculated using the creatinine-based Berlin Initiative Study–1 (BIS1) equation, and to presence/absence of hypertension (systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg). Subjects were analysed for selected SNPs spanning the SLC7A8 and SLC3A2 loci by Sequenom MassARRAY iPLEX platform. Results The most significant SNP at the SLC3A2 (4F2hc) locus was rs2282477-T/C, with carriers of the C-allele having a lower chance to develop hypertension among CKD affected individuals [OR = 0.33 (CI 0.14–0.82); p = 0.016]. A similar association with hypertensive CKD was found for the SLC7A8 (LAT2) rs3783436-T/C, whose C-allele resulted associated with decreased risk of hypertension among subjects affected by CKD [OR = 0.56 (95% CI 0.35–0.90; p = 0.017]. The two variants were predicted to be potentially functional. Conclusions The association between SLC3A2 and SLC7A8 variants to hypertension development in patients with renal failure could be linked to changes in L-DOPA uptake and consequently dopamine synthesis. Although additional research is needed, our study opens new avenues for future basic and translational research in the field of hypertensive CKD.
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