title: Common Variants in LRP2 and COMT Genes Affect the Susceptibility of Gout in a Chinese Population.
abstract: Gout is a common inflammation disease resulting from an increase in serum uric acid. Nearly 70% of uric acid is excreted via the kidneys. To date, evidence for an association between genetic loci and gout is absent, equivocal or not replicated. Our study aims to test variants in two genes abundantly expressed in the kidney, LRP2 and COMT, for their association with uric acid and gout. In total, 1318 Chinese individuals were genotyped for rs2544390 in LRP2 and rs4680 in COMT. These LRP2 and COMT gene polymorphisms showed no significant effect on uric acid (P = 0.204 and 0.188, separately); however, rs2544390 in LRP2 did influence uric acid levels in individuals with BMI ≥ 25 (P = 0.009). In addition, the allele frequency distributions of the two loci showed a significant difference between gout patients and healthy controls. A missense variation in rs4680 (G > A) decreased the risk of gout (OR = 0.77, P = 0.015), whereas the T allele of rs2544390 was associated with gout pathogenesis risk (OR = 1.26, P = 0.020). The present study provides the first evidence for an association between COMT and gout. Rs2544390 in LRP2 only influenced uric acid levels in individuals with BMI ≥ 25, which might explain the discrepant results among previous studies. In addition, we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians.
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Division of Rheumatology and Immunology, Changhai Hospital, Shanghai, China.
authors.forename: Dongbao
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Division of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Chengde
authors.initials: C
authors.lastname: Yang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Jingru
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Qiaoxia
authors.initials: Q
authors.lastname: Qian
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Division of Rheumatology, Taixing People's Hospital, Jiangsu Province, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: He
authors.affiliation: Division of Rheumatology, Taizhou People's Hospital, Jiangsu Province, China.
authors.forename: Hengdong
authors.initials: H
authors.lastname: Ji
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China; Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China.
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China; Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Rheumatology and Immunology, Changhai Hospital, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Rheumatology and Immunology, Changhai Hospital, Shanghai, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Pang
authors.affiliation: Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China; Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
authors.forename: Hejian
authors.initials: H
authors.lastname: Zou
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China; Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China; Division of Rheumatology, Taixing People's Hospital, Jiangsu Province, China; Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China.
authors.forename: Jiucun
authors.initials: J
authors.lastname: Wang
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002681:China; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006073:Gout / Q000097:blood / Q000235:genetics*; D006801:Humans; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014527:Uric Acid / Q000097:blood
chemical_list: C000597357:LRP2 protein, human; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D014527:Uric Acid; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase