Associations between gene polymorphisms in fatty acid metabolism pathway and preterm delivery in a US urban black population.
ABSTRACT There is increasing evidence suggesting that higher intakes of fish or n-3 polyunsaturated fatty acids supplements may decrease the risk of preterm delivery (PTD). We hypothesized that genetic variants of the enzymes critical to fatty acids biosynthesis and metabolism may be associated with PTD. We genotyped 231 potentially functional single nucleotide polymorphisms (SNPs) and tagSNPs in 9 genes (FADS1, FADS2, PTGS1, PTGS2, ALOX5, ALOX5AP, PTGES, PTGES2, and PTGES3) among 1,110 black mothers, including 542 mothers who delivered preterm (<37 weeks gestation) and 568 mothers who delivered full-term babies (≥37 weeks gestation) at Boston Medical Center. After excluding SNPs that are in complete linkage disequilibrium or have lower minor allele frequency (<1%) or call rate (<90%), we examined the association of 206 SNPs with PTD using multiple logistic regression models. We also imputed 190 HapMap SNPs via program MACH and examined their associations with PTD. Finally, we explored gene-level and pathway-level associations with PTD using the adaptive rank truncated product (ARTP) methods. A total of 21 SNPs were associated with PTD (p value ranging from 0.003 to 0.05), including 3 imputed SNPs. Gene-level ARTP statistics indicated that the gene PTGES2 was significantly associated with PTD with a gene-based p value equal to 0.01. No pathway-based association was found. In this large and comprehensive candidate gene study, we found a modest association of genes in fatty acid metabolism pathway with PTD. Further investigation of these gene polymorphisms jointly with fatty acid measures and other genetic factors would help better understand the pathogenesis of PTD.
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ABSTRACT: It is hypothesized that the intake of long-chain polyunsaturated fatty acids (LC-PUFAs) throughout pregnancy is important to maternal health and fetal and infant development. The objective was to evaluate systematically the effect of LC-PUFA supplementation of pregnant women's diets on pregnancy outcomes and growth measures at birth. We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library through August 2005 and also searched the references in reviewed articles for randomized controlled trials (RCTs) comparing LC-PUFA supplementation with placebo or no supplementation. Of 6 included RCTs, only 1 was judged to be at low risk of bias. Supplementation with n-3 LC-PUFAs in these 6 RCTs (1278 infants) was associated with a significantly greater length of pregnancy [weighted mean difference (WMD): 1.57 d; 95% CI: 0.35, 2.78 d; findings stable on sensitivity analysis] than in control subjects. We found no evidence that supplementation influenced the percentage of preterm deliveries, the rate of low-birth-weight infants, or the rate of preeclampsia or eclampsia. We found no significant difference in the 6 RCTs (1278 infants) in birth weight (WMD: 54 g; 95% CI: -3.1, 111 g) and no significant difference in 5 RCTs (1262 infants) in birth length (WMD: 0.23 cm; 95% CI: -0.04, 0.5 cm), but, in 4 RCTs (729 infants), there was a significant increase in head circumference (WMD: 0.26 cm; 95% CI: 0.02, 0.49 cm; significance was lost on sensitivity analysis). n-3 LC-PUFA supplementation during pregnancy may enhance pregnancy duration and head circumference, but the mean effect size is small. The implications of these findings for later growth and development remain to be elucidated.American Journal of Clinical Nutrition 07/2006; 83(6):1337-44. · 6.50 Impact Factor
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ABSTRACT: Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.Lipids in Health and Disease 01/2010; 9:63. · 2.02 Impact Factor
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ABSTRACT: Preterm delivery (PTD) is the leading cause of infant mortality and morbidity worldwide. The etiology of PTD is largely unknown but is believed to be complex, encompassing multiple genetic and environmental determinants. To date, reports of genetic studies on PTD are sparse. We conducted a large-scale case-control study exploring the associations of 426 single-nucleotide polymorphisms with PTD in 300 mothers with PTD and 458 mothers with term deliveries at the Boston Medical Center. Twenty-five candidate genes were included in the final haplotype analysis, and a significant association of F5 gene haplotype with PTD was revealed and remained significant after Bonferroni correction for multiple testing (P=0.025). We applied different statistical algorithms (both Gibbs sampling and expectation-maximization) in reconstructing haplotype phases and different tests (both likelihood ratio test and permutation test) in association analyses, and all yielded similar results. We also performed exploratory ethnicity-specific analyses, which confirmed the consistent findings of the F5 gene across the ethnic groups. Moreover, IL1R2 (P=0.002 in Blacks), NOS2A (P<0.001 in Whites) and OPRM1 (P=0.004 in Hispanics) gene haplotypes were associated with PTD in specific ethnic groups but not at global significance level. In summary, our results underscore the potentially important role of F5 gene variants in the pathogenesis of PTD, and demonstrate the utility of high-throughput genotyping and a haplotype-based approach in dissecting genetic basis of complex traits.Human Molecular Genetics 04/2004; 13(7):683-91. · 7.69 Impact Factor