title: Association of protein Z and factor VII gene polymorphisms with risk of cerebral hemorrhage: a case-control and a family-based association study in a Chinese Han population.
abstract: Protein Z (PZ) and factor (F) VII are two important factors in the clotting pathway which have similar structure, linked function and nearby gene sites. The aims of this study were to investigate whether the common variants of PZ and FVII genes are associated with the risk of cerebral hemorrhage (CH) and to explore the combined effects of PZ and FVII polymorphisms for CH risk. We performed genotyping analysis for two single-nucleotide polymorphisms (SNPs) of FVII (rs510317 and rs6046) and three SNPs of PZ (rs2273971, rs3024718 and rs3024731) both in a population-based case-control study and in a family-based association study. Case-control analysis found no evidence of significant association. But family-based association study revealed that the G allele of PZ rs2273971, and three haplotypes carrying the 'G' allele of PZ rs2273971: haplotype GA, CG and CGA of PZ and FVII genes, all had a significant effect on CH susceptibility (Z = 1.882, P = 0.049; Z = 1.922, P = 0.044; Z = 1.826, P = 0.047; Z = 1.977, P = 0.048, respectively). While, the A allele of PZ rs2273971, and four haplotypes carrying or crossing the 'A' allele of PZ rs2273971: haplotypes CA, ACAA, ACAT and ACAAT of PZ and FVII genes, may confer protection against CH (Z= -1.882, P = 0.049; Z= -2.000, P = 0.045; Z= -2.319, P = 0.020; Z= -2.002, P = 0.045; Z= -2.015, P = 0.043, respectively). This is a first family-based association study providing genetic evidences that PZ and FVII genes, especially PZ rs2273971 are involved in the development of CH in Han-Chinese families.
authors.affiliation: Department of Geriatrics,Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, People's Republic of China. zlzdzlzd@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zeng
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Hu
authors.forename: Qidong
authors.initials: Q
authors.lastname: Yang
authors.forename: Mingming
authors.initials: M
authors.lastname: Ma
authors.forename: Baoqiong
authors.initials: B
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Xia
authors.forename: Hongwei
authors.initials: H
authors.lastname: Xu
authors.forename: Yunhai
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Du
mesh_terms: D000483:Alleles; D044466:Asian People; D001798:Blood Proteins / Q000235:genetics*; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D005167:Factor VII / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: D001798:Blood Proteins; C026080:plasma protein Z; D005167:Factor VII