Polymorphisms of the HDL receptor gene associated with HDL cholesterol levels in diabetic kindred from three populations.
OBJECTIVE
We examined polymorphisms in the HDL receptor, SR-BI, for association with plasma HDL cholesterol levels.


METHODS
Study subjects, including 847 women and 725 men, were from families originally ascertained for type 2 diabetes from Finland, Sweden and Israel. Four common polymorphisms were examined in linear regression analysis: an exon 1 missense (EX1), exon 8 silent (EX8), intron 5 (IVS5) and intron 10 (IVS10) variants.


RESULTS
Genotype combinations for the three polymorphisms in linkage disequilibrium (IVS5, EX8 and IVS10) were found to be associated with HDL-C among women from the Israeli (p = 0.01) and Swedish (p = 0.06) populations. In Finnish women, the association was only apparent after taking into account effect modification by triglyceride levels (p = 0.04). One specific pattern of genotypes, denoted by presence of the IVS5_T and EX8_C alleles, and absence of the IVS10_G allele, was consistently associated with the lowest mean levels of HDL-C in women from all three populations. These same associations were not found in men.


CONCLUSIONS
Polymorphic variation of the SR-BI gene may influence HDL-C levels and act in a sex-dependent manner.
McCarthy
Jeanette J
JJ
San Diego State University, San Diego, CA 92182-4162, USA. mccarthy@mail.sdsu.edu
Lewitzky
Steve
S
Reeves
Cynthia
C
Permutt
Alan
A
Glaser
Benjamin
B
Groop
Leif C
LC
Lehner
Thomas
T
Meyer
Joanne M
JM
D018955:CD36 Antigens / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D007557:Israel / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*; D051116:Receptors, Scavenger; D013548:Sweden / Q000453:epidemiology
D018955:CD36 Antigens; D008076:Cholesterol, HDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger