Mitochondrial DNA variant A4917G, smoking and spontaneous preterm birth.
Spontaneous preterm birth (PTB; <37 weeks gestation) is a major risk factor for neonatal morbidity and mortality. The exact cause of PTB is unknown but oxidative stress may play an important role. Genetic studies have recently begun to elucidate the role of genetic variation in PTB but these studies have overlooked the mitochondrial genome/gene(s) as a plausible PTB candidate. In the present study, we sought to document association between nonsynonymous mitochondrial DNA (mtDNA) variants A4917G, G10398A and T4216C and PTB. We performed a case (PTB; <36 weeks gestation)-control (normal term) analysis of these mtDNA markers and examined their potential interaction with smoking in PTB. A sample of 422 pregnant Caucasian women (220 preterm and 202 terms) was examined for association. Haplogroup T marker A4917G was identified as a possible candidate for association with PTB after adjusting for smoking (OR=1.99 [95% CI 0.93-4.24]) as was T4216C (OR=1.63 [95% CI 0.93-2.83]). No significant multi-locus interactions or interactions with other environmental variables were observed. Our data, although preliminary, support the hypothesis that mitochondrial genome polymorphisms may play a significant role in PTB through an interaction with smoking.
Velez
Digna R
DR
Division of Cardiovascular Medicine, Department of Medicine and Center for Human Genetics Research, 519 Light Hall, Vanderbilt University, Nashville, TN 37232, USA.
Menon
Ramkumar
R
Simhan
Hyagriv
H
Fortunato
Stephen
S
Canter
Jeffery A
JA
Williams
Scott M
SM
D000328:Adult; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006801:Humans; D015999:Multivariate Analysis; D010414:Pennsylvania; D017354:Point Mutation; D011247:Pregnancy; D047928:Premature Birth / Q000235:genetics*; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects*; D013714:Tennessee; D044465:White People / Q000235:genetics
D004272:DNA, Mitochondrial