title: Genetic variants in FH are associated with renal histopathologic subtypes of lupus nephritis: a large cohort study from China.
abstract: Objective Genetic variants in FH (complement factor H) were reported to associate with susceptibility to systemic lupus erythematosus (SLE). This study proposed that the genetic defects of FH in the susceptibility and in the development of lupus nephritis might be different. Methods This study enrolled 334 lupus nephritis patients, 269 SLE patients without clinical renal involvement and 350 controls. Two-step genotyping was performed. First, all the exons of the FH gene were fully sequenced in 100 lupus nephritis patients and 100 healthy controls. Second, genotyping of three common variants reported to be functional, rs1061170, rs800292 and rs6677604, was conducted in all the recruited individuals. Further, analysis of their associations with SLE/lupus nephritis susceptibility and the clinico-pathological parameters in the lupus nephritis group was performed. Results No significant differences were observed in allele and genotype frequencies of the three single nucleotide polymorphisms between lupus patients and controls. There was a significantly higher ratio of CC/CT genotypes of rs1061170 in lupus nephritis patients with class III than in the other two classes (class III vs. class IV vs. class V: 21.0% vs. 9.7% vs. 9.4%; P = .044). The rs6677604-GG genotype was observed to be associated with the absence of anti-ds DNA antibody ( P = .021), and the rs800292-TT genotype was associated with a higher level of circulating C3 ( P = 0.20) in lupus nephritis. Conclusion In an independent cohort, this is the first genetic association analysis focusing on FH genetic variants in Chinese lupus nephritis patients. It was found that the variants in the FH gene might affect the histopathologic subtypes and some clinical features of the disease.
authors.affiliation: 1 Renal Division, Department of Medicine, Peking University First Hospital, P.R. China.|2 Institute of Nephrology, Peking University, P.R. China.|3 Key Laboratory of Renal Disease, Ministry of Health of China, P.R. China.|4 Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, P.R. China.
authors.forename: M
authors.initials: M
authors.lastname: Tan
authors.affiliation: 5 Renal Division, Department of Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.
authors.forename: J-B
authors.initials: JB
authors.lastname: Hao
authors.affiliation: 1 Renal Division, Department of Medicine, Peking University First Hospital, P.R. China.|2 Institute of Nephrology, Peking University, P.R. China.|3 Key Laboratory of Renal Disease, Ministry of Health of China, P.R. China.|4 Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, P.R. China.
authors.forename: H
authors.initials: H
authors.lastname: Chu
authors.affiliation: 6 Institute of Nephrology, Zhongda Hospital, Southeast University, Nanjing, P.R. China.
authors.forename: F-M
authors.initials: FM
authors.lastname: Wang
authors.affiliation: 1 Renal Division, Department of Medicine, Peking University First Hospital, P.R. China.|2 Institute of Nephrology, Peking University, P.R. China.|3 Key Laboratory of Renal Disease, Ministry of Health of China, P.R. China.|4 Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, P.R. China.
authors.forename: D
authors.initials: D
authors.lastname: Song
authors.affiliation: 1 Renal Division, Department of Medicine, Peking University First Hospital, P.R. China.|2 Institute of Nephrology, Peking University, P.R. China.|3 Key Laboratory of Renal Disease, Ministry of Health of China, P.R. China.|4 Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, P.R. China.
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.affiliation: 1 Renal Division, Department of Medicine, Peking University First Hospital, P.R. China.|2 Institute of Nephrology, Peking University, P.R. China.|3 Key Laboratory of Renal Disease, Ministry of Health of China, P.R. China.|4 Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, P.R. China.|7 Department of Nephrology, Peking University International Hospital, Beijing, P.R. China.
authors.forename: F
authors.initials: F
authors.lastname: Yu
authors.affiliation: 8 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, P.R. China.|9 Chinese Academy of Medical Sciences & Peking Union Medical College, P.R. China.|10 Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, P.R. China.
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Li
authors.affiliation: 11 Department of Nephrology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing, PR. China.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.affiliation: 1 Renal Division, Department of Medicine, Peking University First Hospital, P.R. China.|2 Institute of Nephrology, Peking University, P.R. China.|3 Key Laboratory of Renal Disease, Ministry of Health of China, P.R. China.|4 Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing, P.R. China.|12 Peking-Tsinghua Center for Life Sciences, Beijing, P.R. China.
authors.forename: M-H
authors.initials: MH
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000235:genetics; D008181:Lupus Nephritis / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: C493495:CFH protein, human; D017242:Complement Factor H
keywords: FH; SLE; genetic variants; lupus nephritis