Complement and Cardiovascular Risk in Adolescents
Condition: Cardiovascular Disease; Type 2 Diabetes
MeSH terms: Cardiovascular Diseases
Study type: Observational

Summary: 
      This study evaluates how genetic variations in complement, a part of the immune system,
      affect cardiovascular risk in adolescents.
    

Detailed description: 
      Cardiometabolic diseases usually do not produce significant mortality and morbidity until
      adulthood. There is clear evidence, however, that these diseases have their origins in
      childhood and adolescence. With the rising incidence of obesity associated with poorer eating
      and less physical activity in children and adolescents it is important that the investigators
      study these diseases early in their course if the investigators are to prevent future
      cardiometabolic disease. While obesity clearly increases cardiometabolic risk, not all obese
      subjects are at increased risk; approximately 25-30% of obese adults and adolescents are
      metabolically healthy. The complement system is key physiological component in controlling
      inflammation and recent studies have indicated complement plays an important role in
      increasing obesity and cardiometabolic risk. Adults with proven cardiometabolic disease or at
      future risk for cardiometabolic disease have increased levels of the complement components
      C3, C3a-desArg, and C4 compared to healthy, not at risk, control subjects, independent of
      obesity. Increased C3 or C3a-desArg levels in adolescents are associated with increased
      cardiometabolic risk independent of obesity. Two specific single nucleotide polymorphisms
      (SNPs) in the intron for C3, rs11569562 and rs2250656, both with A>G polymorphisms, are
      associated with increased serum C3 levels, and increases in a variety of cardiovascular risk
      factors. No one has investigated how C3 polymorphisms affect risk factors in adolescents. The
      C4 gene has significant copy number variation and increased copy number is associated with
      increased C4 levels. The relationship of C4 gene copy number to cardiometabolic risk has not
      been studied in adults or adolescents. The short-term objectives of this study are to explore
      differences in cardiometabolic risk factors in overweight and obese adolescents with C3
      polymorphisms and also to explore how C4 gene copy number variation affects risk factors. The
      investigators overall hypothesis is that variations in C3 polymorphisms, C4 gene copy number
      or both will have significant impact on cardiometabolic health in overweight and obese
      adolescents. Both traditional and nontraditional cardiometabolic risk markers, including
      measures of body habitus, blood pressure, lipids, vascular function, insulin secretion and
      sensitivity, inflammation, and clotting will be investigated in 100 overweight and obese
      adolescents. The investigators proposed study will help us understand the role of complement
      and its genetics in the development of cardiometabolic risk and in potentially developing
      genetic biomarkers for adolescents at increased risk.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Healthy adolescents
      
Keywords: Complement; endothelial function; insulin sensitivity; adolescents; inflammation