title: PPARD rs2016520 polymorphism and circulating lipid levels connect with brain diseases in Han Chinese and suggest sex-dependent effects.
abstract: The PPARD polymorphisms were shown to be associated with circulating lipoprotein metabolism in various diseases. We aimed to check the contribution of PPARD rs2016520 and lipid concentration to the risk of intracerebral hemorrhages (ICH) and brain tumors (BT) in Han Chinese. A total of 864 participants were included in the case-control study. The melting temperature shift (Tm-shift) method was used for rs2016520 genotyping. Under the recessive model, PPARD rs2016520 was shown to be associated with the risk of ICH (P=0.029, odds ratio (OR)=2.72), specifically in males (P=0.045, OR=3.98). Additionally, we also found that the levels of TC and LDL-C were significantly higher in participants with brain diseases than in the controls (TC: P<0.0001; LDL-C: P<0.0001). Significantly higher HDL-C and lower ApoA-I levels were observed in the male patients with brain diseases (HDL-C: P<0.0001; ApoA-I: P=0.008), in contrast of a higher TG level in female ICH (P=0.023). Subsequent interaction analysis between PPARD rs2016520 and lipoprotein metabolism showed that the LDL-C level was positively correlated with ICH in the rs2016520-AA carriers (P<0.0001), but not in the other genotype carriers (AG or GG, P=0.300). Our results showed that PPARD rs2016520 displayed a strong relationship with ICH risk in the male Han Chinese. The TC and LDL-C levels were positively higher in the patients with brain diseases than in the controls. The levels of TG, HDL-C and ApoA-I were shown to affect brain disease in a gender-dependent model. The genotype rs2016520-AA showed significant interaction with the circulating LDL-C levels in ICH.
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Nie
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Shengjun
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Jikuang
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China.
authors.forename: Zhepei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Huadan
authors.initials: H
authors.lastname: Ye
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China.
authors.forename: Qingxiao
authors.initials: Q
authors.lastname: Hong
authors.affiliation: Department of Neurosurgery, Ningbo First Hospital, Ningbo Hospital of Zhejiang University, Ningbo, Zhejiang 315010, China; Zhou Liangfu Academician Workstation, Neurosurgery Ningbo Branch of Shanghai Huashan Hospital, Ningbo, Zhejiang 315010, China. Electronic address: qinyuecui@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Gao
authors.affiliation: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, China. Electronic address: duanshiwei@nbu.edu.cn.
authors.forename: Shiwei
authors.initials: S
authors.lastname: Duan
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001932:Brain Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D002543:Cerebral Hemorrhage / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D047494:PPAR delta / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012727:Sex Characteristics
chemical_list: D008055:Lipids; D047494:PPAR delta
keywords: Brain tumor; Intracerebral hemorrhage; Lipoprotein; PPARD; rs2016520