Angiotensin-converting enzyme insertion/deletion polymorphism contributes high risk for chronic kidney disease in Asian male with hypertension--a meta-regression analysis of 98 observational studies.
BACKGROUND
Associations between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and chronic kidney disease (CKD) have been extensively studied, with most studies reporting that individuals with the D allele have a higher risk. Although some factors, such as ethnicity, may moderate the association between ACE I/D polymorphisms and CKD risk, gender-dependent effects on the CKD risk remain controversial.


OBJECTIVE
This study investigated the gender-dependent effects of ACE I/D polymorphisms on CKD risk.


METHODS
PubMed, the Cochrane library, and EMBASE were searched for studies published before January 2013.
Cross-sectional surveys and case-control studies analyzing ACE I/D polymorphisms and CKD were included. They were required to match the following criteria: age >18 years, absence of rare diseases, and Asian or Caucasian ethnicity.


METHODS
The effect of carrying the D allele on CKD risk was assessed by meta-analysis and meta-regression using random-effects models.


RESULTS
ETHNICITY [ODDS RATIO (OR): 1.24; 95% confidence interval (CI): 1.08-1.42] and hypertension (OR: 1.55; 95% CI: 1.04-2.32) had significant moderate effects on the association between ACE I/D polymorphisms and CKD risk, but they were not significant in the diabetic nephropathy subgroup. Males had higher OR for the association between ACE I/D polymorphisms and CKD risk than females in Asians but not Caucasians, regardless of adjustment for hypertension (p<0.05). In subgroup analyses, this result was significant in the nondiabetic nephropathy group. Compared with the I allele, the D allele had the highest risk (OR: 3.75; 95% CI: 1.84-7.65) for CKD in hypertensive Asian males.


CONCLUSIONS
The ACE I/D polymorphisms may incur the highest risk for increasing CKD in hypertensive Asian males.
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Chin
C
Lin
School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Hsin-Yi
HY
Yang
Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Chia-Chao
CC
Wu
Division of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
Herng-Sheng
HS
Lee
Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC ; Division of Nephrology, Department of Medicine, Shuang Ho Hospital, Graduate Institute of Clinical Medicine, Taipei Medical University, New Taipei City, Taiwan, ROC.
Yuh-Feng
YF
Lin
Division of Nephrology, Department of Medicine, Cardinal Tien Hospital, School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, ROC.
Kuo-Cheng
KC
Lu
School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Chi-Ming
CM
Chu
School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Fu-Huang
FH
Lin
School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Sen-Yeong
SY
Kao
School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.
Sui-Lung
SL
Su
D000483:Alleles; D044466:Asian People; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics*; D054643:INDEL Mutation; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors; D044465:White People
C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A