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Associations of TERC Single Nucleotide Polymorphisms with Human Leukocyte Telomere Length and the Risk of Type 2 Diabetes Mellitus.

ABSTRACT: Previous Studies have mapped putative loci that may probably regulate leukocyte telomere length (LTL). The strongest associations with LTL were reported for SNP rs12696304 and rs16847897 near the non-coding Ribose Nucleic Acid (RNA) molecule component (TERC) of telomerase enzyme on 3q26. It is unclear whether these identified loci coding functional components of telomerase, exert a similar effect on LTL in other populations or influence risk factors of Type 2 Diabetes Mellitus (T2DM). The present study was performed to: study the influence of TERC polymorphisms on LTL, human telomerase reverse transcriptase (hTERT), indices of obesity and explore the potential associations with T2DM. 225 T2DM patients and 245 age and sex matched controls were studied. Allelic Discrimination (AD) genotyping was utilized to determine TERC SNPs [rs12696304 and rs16847897]. hTERT, adiponectin, Insulin, Homeostasis Model Assessment (HOMA-IR), and LTL were measured. Body Mass Index (BMI) and waist circumference (WC) were recorded. [CC] genotype of rs16847897 was significantly associated with shorter LTL [OR = 1.6, p = 0.004], lower hTERT levels [OR = 0.4, p = 0.006], higher BMI [OR = 2.2, p = 0.006], larger WC [OR = 23.4, p = 0.007] and hypo-adiponectemia [OR = 0.6, p = 0.006]. [GG] genotype of rs12696304 was also significantly associated with shorter LTL [OR = 1.5, p = 0.004], lower hTERT [OR = 0.7, p = 0.006] but with larger WC[OR = 5.3, p = 0.004]. [CC] genotype of rs16847897 and [GG] genotype of rs12696304 together increased the risk of T2DM significantly [OR = 1.7, p = 0.004]. We provide insights connecting a structure that is critically involved in maintaining genomic stability with obesity and T2DM. Given the central role of telomere length in determining telomere function our findings may expand our understanding of the pathological mechanisms underlying age associated conditions such as T2DM.

SUBMITTER: Al Khaldi R

PROVIDER: S-EPMC4705103 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Project description:Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and is associated with chronic local and systemic inflammation and oxidative stress. The enhanced oxidative stress and inflammation have been reported to affect telomere length (TL). Furthermore, a number of SNPs at loci encoding the main components of the telomerase genes, TERT and TERC have been shown to correlate with TL. We aimed to explore the leukocyte TL and genotypes for single nucleotide polymorphisms, rs12696304 (C > G) and rs10936599 (C > T) near TERC in COPD cases and matched healthy controls using q-PCR technologies. Successful assessment of TL was performed for 91 patients and 88 controls. The patients had shorter TL (17919.36 ± 1203.01 bp) compared to controls (21 271.48 ± 1891.36 bp) although not significant (p = 0.137). The TL did not associate with the gender, age, spirometric indexes, smoking habits but tended to correlate negatively with BMI (Rho = - 0.215, p = 0.076) in the controls, but not in COPD patients. The genotype frequencies of the SNPs rs12696304 and rs10936599 were compared between patients and controls and the odds ratios (OR) for developing COPD were calculated. The carriers of the common homozygous (CC) genotypes of the SNPs had higher risk for COPD, compared to carriers of the variants alleles (rs12696304 CG+GG vs. CC; OR: 0.615, 95% CI [0.424-0.894], p = 0.011 and for rs10936599 CT+TT vs. CC OR = 0.668, 95% CI [0.457-0.976], p = 0.044). Analysis on the combined effects of the TERC rs12696304 (C > G) and rs10936599 (C > T) genotypes, CC/CC genotype combination was associated with higher risk for COPD (p < 0.0001) and marginally lower FEV1% pr. in patients with GOLD II (p = 0.052). There was no association between the SNP genotypes and TL. In summary, our results suggest that COPD patients may have shorter TL, and rs12696304 and rs10936599 near TERC may affect the risk of COPD independently of TL.

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Associations of TERC Single Nucleotide Polymorphisms with Human Leukocyte Telomere Length and the Risk of Type 2 Diabetes Mellitus.

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