title: Two-stage association study to identify the genetic susceptibility of a novel common variant of rs2075290 in ZPR1 to type 2 diabetes.
abstract: The SNP of rs964184 in ZPR1 has recently been associated with type 2 diabetes mellitus (T2DM) in Japanese individuals. To comprehensively investigate the association of common variants in ZPR1 with T2DM in Han Chinese individuals, we designed a two-stage case-control study of 3,505 T2DM patients and 6,911 unrelated healthy Han Chinese individuals. A total of 24 single nucleotide polymorphisms (SNPs) were genotyped, and single-SNP association, imputation and gender-specific association analyses were performed. To increase the coverage of genetic markers, we implemented imputation techniques to extend the number of tested makers to 280. A novel SNP, rs2075290, and the previously reported SNP, rs964184, were significantly associated with T2DM in the two independent datasets, and individuals harboring the CC genotype of rs2075290 and GG genotype of rs964184 exhibited higher levels of fasting plasma glucose (FPG) and blood hemoglobin A1c (HbA1c) than individuals of other genotypes. Additionally, haplotype analyses indicated that two haplotype blocks containing rs2075290 or rs964184 were also significantly associated with T2DM. In summary, these results suggest that ZPR1 plays an important role in the etiology of T2DM, and this gene might be involved in abnormal glucose metabolism.
authors.affiliation: Health Science Center, Xi'an Jiaotong University, 76 Yanta West Road, Xi'an, China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Guan
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Division of Biology &Biomedical Sciences, Washington University in Saint Louis, MO, USA.
authors.forename: Tianxiao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Songfang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Qi
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zuo
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Guohong
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Endocrinology and Metabolism, Ninth Hospital of Xi'an, 151 Eastern Section of Southern 2nd Ring Road, Xi'an, China.
authors.forename: Shujin
authors.initials: S
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D002352:Carrier Proteins; D026901:Membrane Transport Proteins; C099746:ZPR1 protein, human