Maternal human telomerase reverse transcriptase variants are associated with preterm labor and preterm premature rupture of membranes.

Premature aging and short telomere lengths of fetal tissues are associated with spontaneous preterm labor (PTL) and preterm premature rupture of membranes (pPROM). Maintenance of telomere length is performed by the enzyme telomerase. Human telomerase reverse transcriptase (hTERT) is a subunit of telomerase, and its dysfunction affects telomere shortening. This study assessed whether maternal or fetal genetic variations in the hTERT gene are associated with PTL or pPROM.A case (PTL or pPROM) control (term birth) genetic association study was conducted in 654 non-Hispanic white mothers (438 term, 162 PTL, 54 pPROM) and 502 non-Hispanic white newborns (346 term, 116 PTB, 40 pPROM). Maternal and fetal DNA samples were genotyped for 23 single nucleotide polymorphisms (SNPs) within the hTERT gene. Allele frequencies were compared between cases and controls, stratified by PTL and pPROM. Maternal and fetal data were analyzed separately.Allelic differences in one SNP of hTERT (rs2853690) were significantly associated with both PTL (adjusted OR 2.24, 95%CI 1.64-3.06, p = 2.32e-05) and with pPROM (adjusted OR 7.54, 95%CI 3.96-14.33, p = 2.39e-07) in maternal DNA. There was no significant association between the hTERT SNPs analyzed and PTL or pPROM in the fetal samples.hTERT polymorphisms in fetal DNA do not associate with PTL or pPROM risk; however, maternal genetic variations in hTERT may play a contributory role in risk of PTL and PPROM