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Title: QUANTITATIVE GENETIC ANALYSIS OF THE METABOLIC SYNDROME IN HISPANIC CHILDREN

Author
item Butte, Nancy
item COMUZZIE, ANTHONY - SWFBR, SAN ANTONIO
item COLE, SHELLEY - SWFBR, SAN ANTONIO
item MEHTA, NITESH - BAYLOR COLLEGE MED
item TEJERO, MARIA - SWFBR, SAN ANTONIO
item BASTARRACHEA, RAUL - SWFBR, SAN ANTONIO
item Smith, O'Brian

Submitted to: Pediatric Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/8/2005
Publication Date: 12/1/2005
Citation: Butte, N.F., Comuzzie, A.G., Cole, S.A., Mehta, N.R., Tejero, M., Bastarrachea, R., Smith, O.E. 2005. Quantitative genetic analysis of the metabolic syndrome in hispanic children. Pediatric Research. 58(6):1243-1248.

Interpretive Summary: Childhood obesity is associated with a clustering of metabolic abnormalities including glucose intolerance, hypertension, and dyslipidemia. This clustering has been referred to as the metabolic syndrome. In this study, we determined the prevalence of the metabolic syndrome in1030 Hispanic children, ages 4-19 y, and studied the effect of environmental and genetic factors on the prevalence of the metabolic syndrome in these children. We measured anthropometry, body composition by DXA, clinical signs, and serum biochemistries using standard techniques. We defined the metabolic syndrome as having three or more metabolic risk components. Risk factor analysis and quantitative genetic analysis were performed. Our results indicated the prevalence of the metabolic syndrome was 20% in the overweight children, or 28% if abnormal liver function was included in the definition of metabolic syndrome. BMI z-score and fasting serum insulin but not sex, age, puberty or body composition had significant influence on the metabolic syndrome. The components of the metabolic syndrome - waist circumference, serum triglycerides, high-density lipoproteins, and systolic blood pressure, serum glucose and liver enzymes - were all shown to be heritable. A common set of genes was shown to affect the components of the metabolic syndrome. This common genetic origin may underlie the clustering of the components of the metabolic syndrome. Our results support a strong genetic contribution to the prevalence of the metabolic syndrome in these Hispanic overweight children.

Technical Abstract: Childhood obesity is associated with a constellation of metabolic derangements including glucose intolerance, hypertension, and dyslipidemia, referred to as the metabolic syndrome. The purpose of this study was to investigate genetic and environmental factors contributing to the metabolic syndrome in Hispanic children. Metabolic syndrome defined as having three or more metabolic risk components was determined in 1030 Hispanic children, ages 4-19 y, from 319 families enrolled in the VIVA LA FAMILIA study. Anthropometry, body composition by DXA, clinical signs, and serum biochemistries were measured using standard techniques. Risk factor analysis and quantitative genetic analysis were performed. Of the overweight children, 20% or 28% if abnormal liver function is included in the definition presented with the metabolic syndrome. Odds ratios for the metabolic syndrome were significantly increased by BMI z-score and fasting serum insulin (P<0.01); independent effects of sex, age, puberty and body composition were not seen. Heritabilities ± SE for waist circumference (h2=0.42 ± 0.08), TG (h2=0.54 ± 0.08), HDL-C (h2=0.64 ± 0.07), SBP (h2=0.32 ± 0.07), glucose (h2=0.62 ± 0.08), and ALT (h2=0.28 ± 0.08) were highly significant (P=5.4 x 10-5 to 3.0 x 10-22). Pleiotropy (a common set of genes affecting two traits) detected between SBP and waist circumference, SBP and glucose, HDL-C and waist circumference, ALT and waist circumference, and TG and ALT may underlie the clustering of the components of the metabolic syndrome. Significant heritabilities and pleiotropy seen for the components of the metabolic syndrome indicate a strong genetic contribution to the metabolic syndrome in overweight Hispanic children.