Parental clinical manifestation association with neonate KLRG1 expression and telomere Programming in a Pakistani Population

Abstract Objective This study investigates the association of parental clinical manifestations on newborn telomere biology and immune senescence markers, utilising 204 parent–newborn triads in Karachi, Pakistan. The demographic data collection was followed by quantification of telomere length (TL) using quantitative PCR (qPCR), while Sanger sequencing was performed to analyse variants in telomerase genes (TERC and TERT). Moreover, flow cytometry was used for the analysis of immune senescence markers (CD57 and KLRG1). Results The study revealed that CD57⁺KLRG1⁺ were significantly overexpressed in newborns from the diseased parent (p = 0.045), and particularly KLRG1⁺ expression was positively correlated with both maternal and paternal TLs (mother: r=0.395; P=0.003, father: r=0.32; P=0.014). Parents with chronic or acute conditions (hypertension, COVID-19) exhibited shorter TLs (mother: 1.36 ± 1.02, 1.08 ± 0.81; father: 1.41 ± 0.91, 1.18 ± 0.98) compared to their newborns (1.48 +1.17, 2.2 ± 1.47). Furthermore, genotypic analysis revealed a predominance of the TERC C/C genotype among newborns of parents with diabetes [16 (79%)] (p > 0.05). In contrast, the TERT gene showed significant associations with diabetes [10 (50%)] and hypertension [9(56%)], with statistical significance (p = 0.00). The parental clinical manifestations may significantly influence newborn immune senescence, enabling the upregulation of KLRG1 markers and associations with telomere length.