A Possible Role for the PPARG Pro12Ala Polymorphism in Preterm Birth (original) (raw)

The links between preterm birth, low birth weight, and adult vascular/metabolic morbidity remain unclear. Genetic susceptibility of babies related to these three conditions might contribute to this long-term association. We tested whether the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor ␥ (PPARG) gene could play a role in birth weight and duration of gestation. We genotyped two independent cross-sectional studies from Northern Ireland (n ‫؍‬ 382 and 620). In combined populations, the PPARG Ala12 allele was associated (P ‫؍‬ 0.03) with lower birth weight, primarily caused by shorter gestational duration (P ‫؍‬ 0.04). The frequency of Ala12 allele carriers was higher (P ‫؍‬ 0.027) in the group of individuals born before term (35%, n ‫؍‬ 60) than in the group of individuals born at term (22%, n ‫؍‬ 942). The odds ratios (95% CI) of preterm birth for Ala12 allele carriers were 1.9 (1.1-3.4), P ‫؍‬ 0.022, and 4.2 (1.9-9.7), P ‫؍‬ 0.0006 (adjusted for sex, maternal age, and study), when considering 37 or 35 weeks of pregnancy as a threshold for preterm birth, respectively. Interestingly, the same allele was also associated with a moderate decreased risk of miscarriages in mothers. In conclusion, the PPARG Pro12Ala polymorphism might represent a genetic susceptibility factor for preterm birth and constitute a link between preterm birth and metabolic diseases later in life. Diabetes 56:494-498, 2007 RESEARCH DESIGN AND METHODS Populations. The Young Hearts (YH) project is a prospective study investigating the development of biological and behavioral risk factors for cardiovascular disease in an adolescent population in Northern Ireland. Details of the study design and sampling procedure have been presented elsewhere (6). Briefly, in 1989-1990, a 2% representative sample of school children aged 12 and 15 years in Northern Ireland (YH3, n ϭ 1,015) was collected. The original 12-year-old population was followed up in 1992-1993 (YH2) with complete data collected on 225 boys and 230 girls (90% response rate). Between 1997 and 1999, all original YH participants were invited to participate in the third screening phase (YH3, age 21-25 years, n ϭ 489), and a blood sample for DNA extraction was taken at that time. A further cross-sectional survey, the Young Hearts 2000 (YH2000), was carried out in 2000. Approximately 2,000 boys and girls aged 12 and 15 years (500 in each of the four age-sex groups) were recruited through postprimary schools. Details of the study design have been presented elsewhere (7). In Northern Ireland, birth records have been computerized since 1971 by the Department of Health and Social Services. Records concerning birth weight and length of gestation were available from this data system. Other perinatal information available included parity, parental age, number of miscarriages, and number of stillbirths. Genomic DNA and data on gestational duration and birth weight were available for 382 and 620 singleton births in YH3 and YH2000, respectively. The prevalence of preterm birth (before 37