Telomere length is maternally inherited and associated with lipid metabolism in Chinese population.
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ABSTRACT:
SUBMITTER: Guo L
PROVIDER: S-EPMC8791204 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Telomere length (TL) is linked to various age-related diseases, but little is known about telomeres in gestational diabetes mellitus (GDM). We surveyed 509 subjects (113 GDM patients and 396 frequency matched controls) in Nanjing Drum Tower Hospital, Jiangsu province of eastern China. Relative telomere length (RTL) of genomic DNA extracted from peripheral blood leukocytes was measured using quantitative polymerase chain reaction (qPCR). Odds ratios (OR) and 95% confidence interval (CI) of GDM risk were calculated across tertiles of RTL using logistic regression model. Lipid parameters during the third trimesters of gestation (after 32 weeks) were collected from medical records. The general linear correlation test was used to explore the associations of lipid parameters with RTL. Our results showed that the RTL in GDM patients were significantly shorter than controls (0.302 ± 0.112 vs. 0.336 ± 0.164, P = 0.046). However, the GDM risk was significantly increased in subjects with median RTL (adjusted OR [aOR]: 1.936, 95% CI: 1.086, 3.453, P = 0.025) and the shortest RTL (aOR: 1.795, 95% CI: 1.004, 3.207, P = 0.048), compared to subjects with longest RTL. We also demonstrated that the lipid ratios (TC/TG, LDL/TG, HDL/TG, LDL/TC, TC/LDL) were significantly associated with RTL among controls. Overall, the present study indicated that attrition of telomeres would increase GDM risk among pregnant women, and the altered lipid levels may play an important role in RTL related GDM risk and pathogenesis.
| S-EPMC6560111 | biostudies-literature
Project description:A recent genome-wide association study has identified an association between leukocyte telomere length (LTL) and a locus at 3q26 that includes TERC. In order to evaluate the effects of the SNPs rs12696304 and rs16847897 near TERC in the population of mainland China, we conducted an association study of LTL focusing on these two candidate SNPs in a sample of 4016 Chinese Han individuals. Multiple linear regression analyses were performed to evaluate the association of LTL with each SNP adjusted for age, gender and diabetes status. In the study, we confirmed the association of SNP rs12696304 and rs16847897 near TERC with LTL in the Chinese Han population (P ? 4.5 × 10(-3) and 9.5 × 10(-5), respectively). Each copy of the major allele of rs12696304 and rs16847897 was associated with a shorter mean telomere length of 0.024 and 0.031 T/S respectively, which is equivalent to about 3 and 4 years of average age-related telomere attrition. Our short report confirmed the effects of SNPs near TERC on LTL in the Chinese Han population for the first time.
| S-EPMC3110055 | biostudies-literature
Project description:We have studied models of telomerase haploinsufficiency in humans and mice to analyze regulation of telomere length and the significance of "set points" in inheritance of telomere length. In three families with clinical syndromes associated with short telomeres resulting from haploinsufficient mutations in TERT, the gene encoding telomerase reverse transcriptase, we asked whether restoration of normal genotypes in offspring of affected individuals would elongate inherited short telomeres. Telomeres were shorter than normal in some but not all genotypically normal offspring of telomerase-mutant parents or grandparents. Analysis of these findings was complicated by heterogeneity of telomere length among individuals, as well as by the admixing of telomeres inherited from affected parents with those inherited from unaffected ("wild-type" TERT) parents. To understand further the inheritance of telomere length, we established a shortened-telomere mouse model. When Tert(+/-) heterozygous mice were successively cross-bred through 17 generations, telomere length shortened progressively. The late-generation Tert(+/-) mice were intercrossed to produce genotypically wild-type Tert(+/+) mice, for which telomere length was characterized. Strikingly, telomere length in these Tert(+/+) mice was not longer than that of their Tert(+/-) parents. Moreover, when successive crosses were carried out among these short-telomere Tert(+/+) offspring mice, telomere length was stable, with no elongation up to six generations. This breeding strategy therefore has established a mouse strain, B6.ST (short telomeres), with C57BL/6 genotype and stable short telomeres. These findings suggest that the set point of telomere lengths of offspring is determined by the telomere lengths of their parents in the presence of normal expression of telomerase.
| S-EPMC2890496 | biostudies-literature
Project description:Telomeres are long DNA repeats and a protein complex at chromosome ends that are essential for genome integrity. Telomeres are very short in patients with dyskeratosis congenita due to germline mutations in telomere biology genes. We compared telomere length in patients with Fanconi anemia, Diamond-Blackfan anemia and Shwachman-Diamond syndrome with telomere length in dyskeratosis congenita. Telomere length was measured in six leukocyte subsets by automated multicolor flow fluorescence in situ hybridization, and age-adjusted using Z-scores (-2.326 = 1(st) percentile) were created. We examined individual data, and used canonical variate analysis for group comparisons and outlier detection. Most dyskeratosis congenita telomere lengths were below the 1(st) percentile, while only 2 Fanconi anemia and one each Diamond-Blackfan anemia and Shwachman-Diamond syndrome were that low. However, Fanconi anemia, Diamond-Blackfan anemia and Shwachman-Diamond syndrome clustered in the bottom half of the normal range. Canonical variate analysis separated dyskeratosis congenita widely from the other three syndromes by the first canonical variable (89.7% of the variance); the second variable (10.0%) separated Diamond-Blackfan anemia, Shwachman-Diamond syndrome, and Fanconi anemia from each other. Overall, unlike in dyskeratosis congenita, telomere lengths in patients with non-dyskeratosis congenita inherited bone marrow failure syndromes were usually in the normal range, albeit shorter than in unaffected individuals. Clinicaltrials.gov identifier: 00027274.
| S-EPMC4281312 | biostudies-literature
Project description:The role of telomere in genomic stability is an established fact. Variation in leukocyte telomere length (LTL) has been considered a crucial factor that associated with age-associated diseases. To elucidate the association between LTL variation and ischemic stroke (IS) risk, we selected ten single nucleotide polymorphisms (SNPs) in three genes (TERC, TERT and RTEL1) that previously reported link to LTL, and genotyped SNPs of these genes in a case-control study. The association between polymorphisms and IS risk were tested by Chi squared test and haplotype analysis. In allele association analysis, allele "C" in rs10936599 of TERC gene and allele "G" in rs2853677 of TERT gene were found to have an increased risk of IS when compared with allele "T" and "A", respectively. Model association analysis showed that genotype "G/A" in the overdominant model and genotypes "G/A" and "A/A" in the dominant model of rs2242652 presented a more likelihood to have IS. Another TERT locus (rs2853677) with genotype "G" was also found IS-related risky in the log-additive model. Taken together, our results suggest a potential association between LTL related TERC, TERT gene variants and ischemic stroke risk.
| S-EPMC5216405 | biostudies-literature
Project description:Purpose:The aim of this study was to investigate the association of telomere length with breast cancer risk. We simultaneously explored the association between telomerase reverse transcriptase gene polymorphisms and telomere length. Methods:We used real-time quantitative polymerase chain reaction to measure relative telomere length (RTL) in genomic DNA extracted from peripheral blood from 183 breast cancer cases and 191 healthy controls. Genotyping was performed using the Sequenom MassARRAY platform. Results:Our results show that breast cancer patients had significantly shorter RTLs than control subjects (p<0.05). When the RTLs were categorized into tertiles, we found that the lowest RTL was significantly associated with increased breast cancer risk compared with the highest RTL (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.40-3.90; p=0.001). Subgroup analyses indicated that risk of breast cancer was also significantly increased in the lowest RTL compared with the highest RTL in age >40 years (OR, 2.41; 95% CI, 1.31-4.43; p=0.005), body mass index ?24 kg/m2 (OR, 2.81; 95% CI, 1.55-5.10; p=0.001), and postmenopausal women (OR, 3.94; 95% CI, 1.63-9.51; p=0.002), respectively. In addition, individuals with the AA genotype of rs2853677 have longer telomeres than those of breast cancer patients with the AG genotype (p=0.011). Conclusion:Our results suggest that shorter RTL was associated with an increased risk of breast cancer. An association was found between the AA genotype of rs2853677 and longer RTLs in the case group. Functional studies are warranted to validate this association and further investigate our findings.
| S-EPMC6310718 | biostudies-literature
Project description:BackgroundSingle nucleotide polymorphisms (SNPs) in telomere-related genes are associated with a high risk of hepatocellular carcinoma (HCC). In this study, we investigated the SNPs of telomere length-related genes and their correlation with HCC risk in the Chinese Han population.Materials and methodsA total of 473 HCC patients and 564 healthy volunteers were recruited. Overall, 42 SNPs distributed in telomere-related genes were selected and identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated.ResultsWe found rs6713088 (OR = 1.27, 95% CI = 1.07-1.52, p = 0.007), rs843711 (OR = 1.29, 95% CI = 1.09-1.54, p = 0.004) and rs843706 (OR = 1.30, 95% CI = 1.09-1.55, p = 0.003) in the ACYP2 gene, rs10936599 (OR = 1.21, 95% CI = 1.02-1.44, p = 0.032) in the TERC gene and rs7708392 (OR = 1.24, 95% CI = 1.00-1.52, p = 0.042) in the TNIP1 gene were associated with high HCC risk (OR > 1). In contrast, rs1682111 (OR = 0.77, 95% CI = 0.64-0.94, p = 0.008) in the ACYP2 gene, rs2320615 (OR = 0.79, 95% CI = 0.64-0.99, p = 0.038) in the NAF1 gene, rs10069690 (OR = 0.75, 95% CI = 0.59-0.96, p = 0.021) and rs2242652 (OR = 0.70, 95% CI = 0.55-0.90, p = 0.004) in the TERT gene were associated with low HCC risk (OR < 1). Based on genotype frequency distributions, rs6713088, rs843645, rs843711 and rs843706 located in the ACYP2 gene as well as rs10936599 in the TERC gene were associated with a high incidence of HCC (p < 0.05). In addition, SNPs in these genes could form a linkage imbalance haplotype. Specifically, the haploid 'GC' formed by rs10069690 and rs2242652 within the TERT gene increased the risk of HCC (p < 0.05).ConclusionSNPs in ACYP2, TERC, TERT and other genes were correlated with HCC risk in the Chinese Han population. These data may provide new insights into early diagnosis and screening of HCC.
| S-EPMC7290267 | biostudies-literature
Project description:IntroductionTelomere length (TL) is generally regarded as a biomarker of aging. TL, which is influenced by sociodemographic factors, has been shown to be inversely associated with morbidity. However, most studies examined the youngest, and whether the findings can be extended to older individuals is less clear. Further, few studies have examined these questions in Chinese older adults. This cross-sectional study examined TL and its associated factors in Chinese aged 75+ years in Hong Kong.MethodsParticipants were from the Mr. and Ms. Osteoporosis cohort. A structured interview on sociodemographic factors and physical measurement was conducted. Frailty and sarcopenia status were respectively determined by Fried's criteria and the Asian Working Group for Sarcopenia definition. TL was measured by a molecular inversion probe-quantitative PCR assay and expressed as a novel telomere/a single copy reference gene (T/S) ratio. Adjusted binary logistic regressions were used to examine the associations between TL and the presence of multimorbidity, age-related diseases, frailty, and sarcopenia.ResultsAmong 555 participants (mean age 83.6 ± 3.8 years, 41.3% females), the mean T/S ratio was 1.01 ± 0.20. Males had a lower T/S ratio (0.97 ± 0.20) compared with females (1.07 ± 0.18) (p < 0.001). A lower education level was related to a longer TL (p = 0.016). Being a current smoker was related to a shorter TL (p = 0.007). TL was not significantly different across categories of age, subjective socioeconomic status, drinking status, physical activity level, and body mass index (p > 0.05). There were no associations between TL and the presence of multimorbidity, diabetes, stroke, cardiovascular diseases, cognitive impairment, frailty, and sarcopenia.ConclusionAmong Chinese aged 75+ years, males had shorter TL compared with females. TL was not associated with age-related diseases, frailty, and sarcopenia in this age group. TL may not be a biological marker of aging among older individuals.
| S-EPMC10652652 | biostudies-literature
Project description:Telomere shortening has been associated with multiple age-related diseases such as cardiovascular disease, diabetes, and dementia. However, the biological mechanisms responsible for these associations remain largely unknown. In order to gain insight into the metabolic processes driving the association of leukocyte telomere length (LTL) with age-related diseases, we investigated the association between LTL and serum metabolite levels in 7,853 individuals from seven independent cohorts. LTL was determined by quantitative polymerase chain reaction and the levels of 131 serum metabolites were measured with mass spectrometry in biological samples from the same blood draw. With partial correlation analysis, we identified six metabolites that were significantly associated with LTL after adjustment for multiple testing: lysophosphatidylcholine acyl C17:0 (lysoPC a C17:0, p-value = 7.1 × 10-6), methionine (p-value = 9.2 × 10-5), tyrosine (p-value = 2.1 × 10-4), phosphatidylcholine diacyl C32:1 (PC aa C32:1, p-value = 2.4 × 10-4), hydroxypropionylcarnitine (C3-OH, p-value = 2.6 × 10-4), and phosphatidylcholine acyl-alkyl C38:4 (PC ae C38:4, p-value = 9.0 × 10-4). Pathway analysis showed that the three phosphatidylcholines and methionine are involved in homocysteine metabolism and we found supporting evidence for an association of lipid metabolism with LTL. In conclusion, we found longer LTL associated with higher levels of lysoPC a C17:0 and PC ae C38:4, and with lower levels of methionine, tyrosine, PC aa C32:1, and C3-OH. These metabolites have been implicated in inflammation, oxidative stress, homocysteine metabolism, and in cardiovascular disease and diabetes, two major drivers of morbidity and mortality.
| S-EPMC6690953 | biostudies-literature
Project description:Extensive mammographic density is a strong risk factor for breast cancer, but may also be an indicator of biological age. In this study we examined whether mammographic density is related to blood telomere length, a potential marker of susceptibility to age-related disease. We measured mammographic density by a computer assisted method and blood telomere length using a validated PCR method. Urinary malondialdehyde (MDA), a marker of lipid peroxidation, was measured in 24 hour urine collections. In the 342 women examined telomere length was negatively correlated with age, was lower in postmenopausal compared to premenopausal women and in smokers compared to non-smokers, and was positively correlated with urinary MDA. Telomere length was not associated with percent mammographic density or dense area, before or after adjustment for risk factors and MDA. However, there was a significant interaction between telomere length and MDA in their association with mammographic density. At lower levels of MDA, mammographic density and telomere length were inversely associated; while at high levels of MDA, there was evidence of a J-shaped association between mammographic density and telomere length. Further work is need to replicate these results and to examine the association of mammographic density with age-related chronic disease and mortality.
| S-EPMC5517610 | biostudies-literature