A functional common polymorphism of the ABCB1 gene is associated with chronic kidney disease and hypertension in Chinese.
BACKGROUND
Permeability glycoprotein is encoded by the ATP-binding cassette B1 gene (ABCB1) and is an extruder of toxic metabolites in the kidney. A functional common polymorphism (C3435T, rs1045642) in the human ABCB1 gene has been found to be associated with allograft outcome in kidney transplant patients. In this study, we investigated the association of the C3435T polymorphism with renal function and blood pressure (BP) in 2 Chinese populations.


METHODS
The discovery and replication populations were recruited from a mountainous area (Zhejiang Province) and a newly urbanized suburban area (Shanghai), respectively. We genotyped all subjects using the ABI SNapShot method. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate <60 ml/min × 1.73 m(2) or 24-hour urinary albumin excretion ≥30 mg.


RESULTS
In the discovery population of 1,987 subjects, after adjustment for covariables, TT homozygosity (n = 217) was associated with a higher risk of CKD (n = 369; odds ratio (OR) = 1.73; P = 0.003) and with higher systolic BP (+3.1 mm Hg; P = 0.03) and pulse pressure (+3.4 mm Hg; P = 0.001). These associations were dependent on age (Pint ≤ 0.05). In subjects aged ≥60 years (n = 374), the corresponding OR or difference was 2.40 for CKD, 15.1 mm Hg for systolic BP, and 12.4 mm Hg for pulse pressure (P < 0.001). In similar adjusted analyses in the replication population of 2,427 elderly (≥60 years) subjects, TT homozygosity was also associated with a higher risk of CKD (OR = 1.39; P = 0.02) and an enhanced association of hypertension with CKD (OR = 1.50; P = 0.04).


CONCLUSIONS
The ABCB1 C3435T polymorphism might predict CKD, especially in the elderly.
Centre for Epidemiological Studies and Clinical Trials, Shanghai Key Lab of Hypertension, Shanghai Institute of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Ming
M
Liu
Yan
Y
Li
Lorena
L
Citterio
Qi-Fang
QF
Huang
Wei-Fang
WF
Zeng
Chang-Sheng
CS
Sheng
Fang-Fei
FF
Wei
Qian
Q
Dong
Ge-Le
GL
Li
Yuan-Yuan
YY
Kang
Lu
L
Zhang
Ting-Yan
TY
Xu
Jing-Jing
JJ
Li
Jie
J
Song
Paolo
P
Manunta
Ji-Guang
JG
Wang
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D002648:Child; D002681:China / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate / Q000235:genetics; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D012494:Sampling Studies; D012680:Sensitivity and Specificity
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015415:Biomarkers
ABCB1; albuminuria; blood pressure; chronic kidney disease; genetic polymorphism; hypertension; renal function.