Mol. Hum. Reprod. Advance Access published online on January 12, 2009
Molecular Human Reproduction, doi:10.1093/molehr/gan078
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Proinflammatory cytokine polymorphisms and the risk of preterm birth and low birth weight in a Japanese population
1Department of Public Health, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan 2Department of Epidemiology, National Institute of Public Health, Wako 351-0197, Japan 3Department of Obstetrics and Gynecology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan 4Department of Heath Science, Asahikawa Medical College, Asahikawa 078-8510, Japan
5 Correspondence address. Department of Epidemiology, National Institute of Public Health, Wako 351-0197, Japan. Tel: +81-48-458-6115; Fax: +81-48-469-2677; E-mail: sata{at}niph.go.jp
Pregnancy and parturition involve a complex and poorly understood molecular and biological interplay between mother and fetus. Inflammatory cytokines have been reported to be associated with fetal growth and parturition. The aim of this study was to examine whether common proinflammatory cytokine polymorphisms are associated with preterm birth (PTB), low birth weight (LBW) or intrauterine growth restriction (IUGR) in a Japanese population. We assessed a consecutive series of 414 women who had singleton deliveries in Sapporo, Japan between 2001 and 2005. Genotyping of IL1A –889C/T, +4845G/T (A114S), IL1B –511C/T, –31C/T, IL2 -384T/G and IL6 -634C/G polymorphisms was determined by an allelic discrimination assay. The risk of PTB significantly increased in women carrying the IL1A -889T allele (CC genotype [reference]; CT genotype, OR: 2.5; 95% CI: 1.4-4.8; CT+TT genotypes [dominant genotype model], OR: 2.5, 95% CI: 1.3-4.6). Similarly, the risk of PTB significantly increased in women carrying the IL1A +4845T allele (GG genotype [reference]; GT genotype, OR: 2.4, 95% CI: 1.3-4.4; GT+TT genotypes [dominant genotype model], OR: 2.3, 95% CI: 1.2-4.2). The frequency of the IL1A TT haplotype in mothers with PTB was significantly higher than in mothers who had a term birth (TB) (p<0.001), whereas the frequency of the IL1A CG haplotype in mothers who had a PTB was significantly lower (p<0.001). Our findings suggest that the polymorphisms and haplotypes in the IL1A gene are associated with preterm birth in Japanese women.
Key Words: cytokines/growth factors/gene mutations/haplotype/preterm birth/low birth weight
Submitted on July 21, 2008; resubmitted on December 10, 2008; accepted on December 17, 2008.