Effects of G994T in the Lp-PLA2 gene on the plasma oxidized LDL level and carotid intima-media thickness in Japanese: the Shimane study.
BACKGROUND
A single-nucleotide polymorphism (SNP), G994T, in the lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) gene is known to have a potent influence on the activity of the enzyme. As this enzyme hydrolyzes oxidized low-density lipoprotein (oxLDL), which is an important player in atherogenesis, the present study evaluated effects of the G994T genotype on the oxLDL level as well as on intima media thickness (IMT) in vivo.


METHODS
Participants of a health examination (1,307 in total) were recruited from two rural communities in Shimane, Japan. Genotyping was performed by an allele-specific PCR and the TaqMan method. The oxLDL level was determined by an enzyme immunoassay.


RESULTS
The minor allele (994T) frequency (0.19) in the studied populations was consistent with previous reports on Japanese. The 994T allele increased the plasma oxLDL/LDL ratio in a recessive manner, whereas 994T had a codominant effect on the Lp-PLA(2) activity. A multivariate analysis revealed that age and the G994T genotype had independent effects on the oxLDL/LDL level. By contrast, the G994T genotype was not associated with IMT. All of these results were reproducible in the two independent populations studied.


CONCLUSIONS
G994T influenced plasma LDL oxidation. Further studies on the effect of this polymorphism in cardiovascular diseases are warranted.
Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan.
Tao
T
Wang
Kenji
K
Karino
Masayuki
M
Yamasaki
Yan
Y
Zhang
Junichi
J
Masuda
Shuhei
S
Yamaguchi
Kuninori
K
Shiwaku
Toru
T
Nabika
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002339:Carotid Arteries / Q000033:anatomy & histology*; D006801:Humans; D007564:Japan; D008077:Lipoproteins, LDL / Q000097:blood*; D020641:Polymorphism, Single Nucleotide; D017539:Tunica Intima / Q000033:anatomy & histology*; D017540:Tunica Media / Q000033:anatomy & histology*
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase