Associations Between Telomere Attrition, Genetic Variants in Telomere Maintenance Genes, and Non-Small Cell Lung Cancer Risk in the Jammu and Kashmir Population of North India

BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk. METHODS: We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR. RESULTS: Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values = 0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values = 0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p = 0.0004). CONCLUSION: This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings

A Replication Study of ND3 rs2853826 association with Type 2 Diabetes in North Indian Population

Type 2 Diabetes (T2D) is a complex disease and genetic is one of factor contributing to its pathogenesis. Both decreased body sensitivity to insulin and defects in insulin production are involved in T2D development. ND3 is one of the subunit of complex I which is located in inner mitochondrial membrane of mitochondria. Mitochondrial activity can regulate insulin sensitivity and insulin production. Further, variations in mitochondrial DNA have been shown to raise the risk of T2D. In this study, we replicated the association of ND3 rs2853826 with T2D in a total of 1759 samples (684 T2D cases and 1075 healthy controls) belonging to North India. We observed that ND3 rs2853826 is significantly associated with TD in the studied population and the estimated odds ratio (OR) is 1.65 (1.33 - 2.05 at 95% CI). Thus, our findings replicate and support earlier studies implicating the association of ND3 gene with T2D in Indian population

MACF1 gene variant rs2296172 is associated with type 2 diabetes susceptibility in the Bania population group of Punjab - India

Microtubule Actin Cross linking Factor 1 (MACF1) gene variant rs2296172 has been associated with Type 2 Diabetes (T2D). However, this variant has never been evaluated as such in Indian populations. We replicated this variant in pooled population of Northwest India and specifically in an endogamous caste group, Bania  of Punjab, India. We genotyped variant rs2296172 by Taqman allele discrimination assay in 651 T2D patients and in 568 healthy controls from Northwest India. The association of the SNP with T2D was evaluated by case - control association study design. The SNP rs2296172 of MACF1 was found to be significantly associated with T2D with p value = 0.009 in Northwest Indian population but allelic distribution was observed to be deviated from Hardy-Weinberg equilibrium (HWE). Assuming population stratification the most plausible cause, we further evaluated the samples belonging to Bania caste group from Punjab, India. We observed significant association of this SNP with T2D with OR = 1.71 (1.03-2.83) at 95%CI, (p =0.03) and sample set following HWE. MACF1 variant rs2296172 was found to be associated with T2D in endogamous ethnic population group (Bania) of Punjab, India. Deviation from Hardy-Weinberg equilibrium in the pooled population group from Northwest India, underlines that Indian population sub structure exists and may have implications in association studies. Thus, ideal case - control association study design in Indian populations is to evaluate endogamous population groups rather than the conventional practice of pooling samples based on geography or linguistic affinities only

Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India

Abstract Background Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk. Methods We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR. Results Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values = 0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values = 0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p = 0.0004). Conclusion This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings