Role of genetic factors (CETP gene Taq I B polymorphism and Apo A-I gene Msp I polymorphism) in serum HDL-C levels in women.
OBJECTIVE
Plasma high density lipoprotein cholesterol (HDL-C) levels are determined by a variety of environmental and genetic factors. The cholesteryl ester transfer protein (CETP) and apolipoprotein A-I (Apo A-I) are considered to be associated with HDL-C metabolism. The aim of this study was to investigate the relationship between the CETP gene Taq I B and Apo A-I gene Msp I polymorphisms and plasma lipid levels taking into account environmental factors, and to determine the combined effects of these polymorphisms on HDL-C levels in Japanese women.


RESULTS
The study involved 270 Japanese women aged 30-69 years. We found a significant association between the CETP genotypes and HDL-C levels (p=0.0020), which were also associated with the Apo A-I gene (M1) polymorphism. Stepwise multiple regression analysis revealed that both the CETP Taq I B and Apo A-I gene (M1) genotypes were independent predictive variables. The strength of the association between the Apo A-I (M1) subgroup and HDL-C levels was reduced in the subjects with a high Body Mass Index (BMI). The combination of genotypes provided more detailed information about HDL-C levels. The "high risk" combination of the M1+ (M1+/+) and B1B1 genotypes was associated with the lowest HDL-C level (1.52+/-0.36 mmol/L), and the "low risk" combination of the M1- (M1+/- or M1-/-) and B2B2 genotypes was associated with the highest HDL-C levels (2.06+/-0.34 mmol/L).


CONCLUSIONS
Our results suggest that the combination of the two polymorphisms influences HDL-C levels in women, and that the association between genetic factors and HDL-C levels is altered by environmental factors. They may also help to detect individuals with low HDL-C levels at high risk for coronary artery syndrome.
Motohashi
Y
Y
Department of Internal Medicine, Keio University School of Medicine, Japan.
Maruyama
T
T
Murata
M
M
Nakano
S
S
Maruyama
C
C
Kyotani
S
S
Tsushima
M
M
Saruta
T
T
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000235:genetics*; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood* / Q000235:genetics; D019003:Deoxyribonuclease HpaII / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D005260:Female; D005838:Genotype; D006023:Glycoproteins; D006801:Humans; D007564:Japan; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D015183:Restriction Mapping; D012907:Smoking / Q000378:metabolism
D016632:Apolipoprotein A-I; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D006023:Glycoproteins; D019003:Deoxyribonuclease HpaII; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases