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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2010

Open Access 01-12-2010 | Research article

Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis

Authors: Yi-Chu Liao, Hsiu-Fen Lin, Yuh-Cherng Guo, Ming-Lung Yu, Ching-Kuan Liu, Suh-Hang Hank Juo

Published in: BMC Medical Genetics | Issue 1/2010

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Abstract

Background

The phosphodiesterase 4D (PDE4D) gene was reported as a susceptibility gene to stroke. The genetic effect might be attributed to its role in modulating the atherogenic process in the carotid arteries. Using carotid intima-media thickness (IMT) and plaque index as phenotypes, the present study sought to determine the influence of this gene on subclinical atherosclerosis.

Methods

Carotid ultrasonography was performed on 1013 stroke-free subjects who participated in the health screening programs (age 52.6 ± 12.2; 47.6% men). Genotype distribution was compared among the high-risk (plaque index ≥ 4), low-risk (index = 1-3), and reference (index = 0) groups. We analyzed continuous IMT data and further dichotomized IMT data using mean plus one standard deviation as the cutoff level. Because the plaque prevalence and IMT values displayed a notable difference between men and women, we carried out sex-specific analyses in addition to analyzing the overall data. Rs702553 at the PDE4D gene was selected because it conferred a risk for young stroke in our previous report. Previous young stroke data (190 cases and 211 controls) with an additional 532 control subjects without ultrasonic data were shown as a cross-validation for the genetic effect.

Results

In the overall analyses, the rare homozygote of rs702553 led to an OR of 3.1 (p = 0.034) for a plaque index ≥ 4. When subjects were stratified by sex, the genetic effect was only evident in men but not in women. Comparing male subjects with plaque index ≥ 4 and those with plaque index = 0, the TT genotype was over-represented (27.6% vs. 13.4%, p = 0.008). For dichotomized IMT data in men, the TT genotype had an OR of 2.1 (p = 0.032) for a thicker IMT at the common carotid artery compared with the (AA + AT) genotypes. In women, neither IMT nor plaque index was associated with rs702553. Similarly, SNP rs702553 was only significant in young stroke men (OR = 1.8, p = 0.025) but not in women (p = 0.27).

Conclusions

The present study demonstrates a sex-differential effect of PDE4D on IMT, plaque index and stroke, which highlights its influence on various aspects of atherogenesis.
Appendix
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Metadata
Title
Sex-differential genetic effect of phosphodiesterase 4D (PDE4D) on carotid atherosclerosis
Authors
Yi-Chu Liao
Hsiu-Fen Lin
Yuh-Cherng Guo
Ming-Lung Yu
Ching-Kuan Liu
Suh-Hang Hank Juo
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2010
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-11-93

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