Article

American Journal of Hypertension 2009; 22, 7, 742–747. doi:10.1038/ajh.2009.70

Effects of G994T in the Lp-PLA2 Gene on the Plasma Oxidized LDL Level and Carotid Intima-Media Thickness in Japanese: The Shimane Study

Tao Wang1,2,3, Kenji Karino4, Masayuki Yamasaki5, Yan Zhang6, Junichi Masuda7,8, Shuhei Yamaguchi8,9, Kuninori Shiwaku5,8 and Toru Nabika1,8

  1. 1Department of Functional Pathology, Shimane University School of Medicine, Izumo, Japan
  2. 2The Research Project Promotion Institute, Shimane University, Matsue, Japan
  3. 3Department of Nephrology, the 4th Affiliated Hospital of HeBei Medical University, ShiJiangZhuang, China
  4. 4Central Laboratory of the University Hospital, Shimane University School of Medicine, Izumo, Japan
  5. 5Department of Environmental and Preventive Medicine, Shimane University School of Medicine, Izumo, Japan
  6. 6Department of Dermatology, Shimane University School of Medicine, Izumo, Japan
  7. 7The Third Department of Internal Medicine, Shimane University School of Medicine, Izumo, Japan
  8. 8The Shimane Institute of Health Science, Izumo, Japan
  9. 9Department of Laboratory Medicine, Shimane University School of Medicine, Izumo, Japan

Correspondence: Toru Nabika, (nabika@med.shimane-u.ac.jp)

Received 14 November 2008; First Decision 6 February 2009; Accepted 19 March 2009; Published online 16 April 2009.

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Abstract

Background

 

A single-nucleotide polymorphism (SNP), G994T, in the lipoprotein-associated phospholipase A2 (Lp-PLA2) 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-PLA2 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.

American Journal of Hypertension 2009; doi:10.1038/ajh.2009.70

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