title: MDR1 gene polymorphisms are associated with glucocorticoid-induced avascular necrosis of the femoral head in a Chinese population.
abstract: P-glycoprotein (P-gp) is present in various tissue cells, required for the pumping of lipophilic drugs (including glucocorticoids) out of cells. We hypothesized that polymorphisms in the P-gp encoding gene (multidrug-resistant transporter-1 [MDR1]) are related to individual differences in glucocorticoid sensitivity and the development of glucocorticoid-induced avascular necrosis of the femoral head (GANFH). In this case-control study, we genotyped three known single-nucleotide polymorphisms (SNPs: C1236T, G2677T/A, and C3435T) within the MDR1 gene in 662 Chinese subjects. Statistically significant differences between GANFH patients and either healthy controls or glucocorticoid-resistant patients (non-GANFH) were found for the T allele or TT genotype of C3435T. The haplotype TTT, composed of these three SNPs, exhibited a significant association with the disease. No associations were identified between C1236T or G2677T/A and GANFH. Our results suggest that the C3435T polymorphism of the MDR1 gene is associated with susceptibility to GANFH in a Chinese population.
authors.affiliation: 1 Department of Orthopedics, Sir Run Run Shaw Hospital, Zhejiang University , Hangzhou, China .
authors.forename: Yun
authors.initials: Y
authors.lastname: Xue
authors.forename: Zhan-Qin
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: Dun
authors.initials: D
authors.lastname: Hong
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Hai-Xiao
authors.initials: HX
authors.lastname: Chen
authors.forename: Shun-Wu
authors.initials: SW
authors.lastname: Fan
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics / Q000706:statistics & numerical data; D016022:Case-Control Studies; D005260:Female; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D005938:Glucocorticoids