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鉴定TERC和TERT基因中的多态性等位基因,重新编程新生儿的端粒以及与父母健康状况相关的遗传端粒。

Identification of polymorphic alleles in TERC and TERT gene reprogramming the telomeres of newborn and legacy with parental health.

作者信息

Farrukh Sadia, Baig Saeeda, Hussain Rubina, Imad Rehan, Kulsoom Ome, Yousaf Rana Mehreen

机构信息

Department of Biochemistry, Ziauddin University, Karachi, Pakistan.

Department of Community Health Sciences, The Agha Khan University, Karachi, Pakistan.

出版信息

Saudi J Biol Sci. 2024 Feb;31(2):103897. doi: 10.1016/j.sjbs.2023.103897. Epub 2023 Dec 12.

Abstract

Telomere and telomerase genes (TERC and TERT) highlighted many novel genetic polymorphisms related to common diseases. This study explored the polymorphic alleles of TERC and TERT gene in parents-newborn (triad) and its association with telomere length (TL) and parental diseases (mother: Gestational Diabetes Mellitus (GDM), Preeclampsia, fathers: Diabetes, Hypertension). In this cross-sectional study, the blood samples (n = 612) were collected from parents-newborn triad (204 each) for TL (T/S ratio) quantification by using qPCR, and gene (TERC and TERT) polymorphism was detected by Sanger sequencing. The correlation analysis was used to find an association between paternal TL (T/S ratio) and newborn TL. The multivariate linear regression was applied to determine the effect of parents genes and diseases on newborn TL. A positive association (r = 0.42,0.39) (p < 0.0001) among parents and newborn TL was observed. In the diseased group, both TERC (rs10936599) and TERT (rs2736100) genes had a high frequency of allele C in newborns (OR = 0.94, P = 0.90, OR = 4.24, P = 0.012). However, among parents, TERT gene [Mother CC (B = 0.575; P = 0.196), Father CC (B = -0.739; P = 0.071)] was found significant contributing factor for Newborn TL. Diseased parents with T/T and A/C genotypes had longer newborn TL (2.82 ± 2.43, p < 0.022; 1.80 ± 1.20, p < 0.00) than the C/C genotype. Therefore, the study, confirmed that major allele C of TERC and TERT genes is associated with smaller TL in diseased parents-newborns of the targeted population.

摘要

端粒和端粒酶基因(TERC和TERT)揭示了许多与常见疾病相关的新型基因多态性。本研究探讨了父母-新生儿三联体中TERC和TERT基因的多态性等位基因及其与端粒长度(TL)和父母疾病(母亲:妊娠期糖尿病(GDM)、子痫前期;父亲:糖尿病、高血压)的关联。在这项横断面研究中,从父母-新生儿三联体(各204例)采集血样(n = 612),通过qPCR定量TL(T/S比值),并通过桑格测序检测基因(TERC和TERT)多态性。采用相关性分析来寻找父亲TL(T/S比值)与新生儿TL之间的关联。应用多元线性回归来确定父母基因和疾病对新生儿TL的影响。观察到父母与新生儿TL之间存在正相关(r = 0.42,0.39)(p < 0.0001)。在患病组中,新生儿的TERC(rs10936599)和TERT(rs2736100)基因的等位基因C频率均较高(OR = 0.94,P = 0.90,OR = 4.24,P = 0.012)。然而,在父母中,发现TERT基因[母亲CC(B = 0.575;P = 0.196),父亲CC(B = -0.739;P = 0.071)]是新生儿TL的重要影响因素。患有疾病的父母中,T/T和A/C基因型的新生儿TL比C/C基因型更长(2.82±2.43,p < 0.022;1.80±1.20,p < 0.00)。因此,该研究证实,在目标人群的患病父母-新生儿中,TERC和TERT基因的主要等位基因C与较短的TL相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e49/10772381/1a02eedfcd75/gr1.jpg

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