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.
Highlights
Telomeres are tandem TTAGGG repeats that cap the ends of our chromosomes preventing chromosomal fusions and genomic instability [1, 2]
Since the link between shorter Leukocyte Telomere Length (LTL) and obesity is well documented we propose that single nucleotide polymorphisms (SNPs) near telomeric repetitions (TERC) could affect the degree of obesity, as well as obesity related adipocytokines such as adiponectin (AdipoQ)
Diagnosis of Type 2 Diabetes Mellitus (T2DM) was based on World Health Organization (WHO) criteria [11]. 245 (111 females and 134 males) age- and sex- matched healthy subjects were enrolled from the Kuwait Blood Bank Center
Summary
Telomeres are tandem TTAGGG repeats that cap the ends of our chromosomes preventing chromosomal fusions and genomic instability [1, 2]. A number of recent genome-wide association studies (GWAS) identified common single nucleotide polymorphisms (SNPs) near TERC associated with LTL in European, American, and Chinese populations [7, 9, 10]. The strongest associations with LTL were reported for SNPs rs12696304 and rs16847897 near TERC on 3q26 [7, 9, 10] It is unclear whether the locus identified in Europeans, American, and Chinese exerts a similar effect on LTL in the Arab population and in the Kuwaiti population. None of the earlier studies attempted to explore the effect of such SNPs on serum human telomerase reverse transcriptase (hTERT) levels. This study aims at exploring the associations, between the two major SNPs near TERC [rs16847897 and rs12696304], LTL, and hTERT levels in the Kuwaiti population. We aim to investigate the potential associations of these SNPs with the incidence of T2DM
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