Genetic Modulation on the Relationship of Low Birth Weight to Metabolic Syndrome

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DESCRIPTION (provided by applicant): Low birth weight, an indicator of intrauterine growth restriction, has been demonstrated to be associated with adult cardiovascular (C-V) disease, type 2 diabetes and metabolic syndrome components, including body fatness, insulin resistance measures, blood pressure, and lipoproteins. The interrelationship of low birth weight to multiple components of the metabolic syndrome as a complex entity and the underlying genetic factors can be elucidated further using an advanced sophisticated statistical method like path analysis. The Specific Aims of the proposed research are 1) to examine the impact of low birth weight on metabolic syndrome components by using a path analysis model, longitudinally and cross-sectionally by growth periods, in black versus white individuals, and 2) to investigate the modifying effects of relevant candidate genes on the relationship of low birth weight to longitudinal trends of metabolic syndrome components from childhood to adulthood. These specific aims will be examined using existing phenotypes and candidate gene genotype data available in the Bogalusa Heart Study, a long-term biracial (65% white, 35% black) community-based study of the Natural History of C-V Disease beginning in childhood, since 1973. Study Cohort I for cross-sectional analyses by growth periods consists of 6,051 individuals who have State birth certificate information and metabolic syndrome components; Cohort II for longitudinal analyses consists of 2,775 individuals who have data on birth weight and serial measurements of metabolic syndrome components measured at least 2 times each in childhood and in adulthood during 1973-2008, with 16,276 observations; Cohort III (n=1,447, 990 whites, 457 blacks) for genetic analyses is a subset of Cohort II with candidate gene genotype data available. Single nucleotide polymorphisms (SNPs, n=618) in 21 candidate genes related to both birth weight and metabolic syndrome will be analyzed as individual SNPs, haplotypes and gene-gene interactions. Path analyses will be performed cross-sectionally and longitudinally to examine the relationship of birth weight to the metabolic syndrome components by haplotype groups. The modulating effect of the candidate genes will be tested in terms of significant differences in the path analysis parameters between haplotype groups. The genetic loci identified in the proposed research will provide a basis for further research on the pleiotropic effects and additive effects of multigenes, and more dense sequencing in significant candidate genes in subjects who have a low birth weight and extremes values of the metabolic syndrome variables. This has important implications for improving prenatal care and developing strategies beginning early to prevent adult C-V disease. PUBLIC HEALTH RELEVANCE: Low birth weight is an indicator of baby growth restriction before birth, and associated with adult heart disease, diabetes and risk factors such as obesity, high blood pressure, high cholesterol and high blood sugar. The findings from this research has important implications for improving prenatal care and developing strategies beginning early to prevent adult heart disease.