Evidence for distinct genetic effects on obesity and lipid-related CVD risk factors in diabetic compared to nondiabetic American Indians: the Strong Heart Family Study.
BACKGROUND
The relationship between diabetes and increased cardiovascular disease (CVD) risk is well established. Previous data from the Strong Heart Family Study (SHFS) have demonstrated significant heritabilities for CVD risk factors and implicated diabetes as an important predictor of several of the phenotypes in three large groups of American Indians in Arizona (AZ), Oklahoma (OK), and the Dakotas (DK). However, the genetic architecture of this relationship is not well understood. The purpose of the present paper is to determine whether the genetic effects on CVD risk factors in the SHFS are different in diabetic and nondiabetic individuals.


METHODS
Approximately 950 men and women, 18 years or older, in 32 extended families, were examined between 1997 and 1999. Interaction between genotype and diabetes status was estimated for nine CVD risk factors [body fat mass (FAT), body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), log-transformed fibrinogen, log-transformed triglycerides, log-transformed urinary albumin : creatinine ratio (LACR), plasminogen activator inhibitor 1 (PAI-1), systolic blood pressure (SBP), and waist-to-hip ratio (WHR)], using a maximum likelihood variance decomposition technique.


RESULTS
We found evidence that genetic factors influencing BMI, FAT, log-transformed triglycerides, HDL-C, and WHR are differentially expressed in individuals with diabetes compared to those without diabetes.


CONCLUSIONS
Thus, in the environmental and genetic milieu of diabetes, there may be distinct genetic determinants of various CVD risk factors.
North
Kari E
KE
Department of Epidemiology, University of North Carolina, Chapel Hill, Bank of America Center, North Carolina 27514-3628, USA. kari_north@unc.edu
MacCluer
Jean W
JW
Williams
Jeff T
JT
Welty
Thomas K
TK
Best
Lyle G
LG
Lee
Elisa T
ET
Fabsitz
Richard R
RR
Howard
Barbara V
BV
D000368:Aged; D002318:Cardiovascular Diseases / Q000208:ethnology* / Q000235:genetics*; D003920:Diabetes Mellitus / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007198:Indians, North American / Q000235:genetics* / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009765:Obesity; D010641:Phenotype; D012307:Risk Factors