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Published in: Rheumatology International 3/2016

01-03-2016 | Original Article - Genes and Disease

WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients

Authors: Bing Lan, Peng Chen, Mutu Jiri, Na He, Tian Feng, Kai Liu, Tianbo Jin, Longli Kang

Published in: Rheumatology International | Issue 3/2016

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Abstract

Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms’ effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations.
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Literature
1.
go back to reference Robinson PC, Horsburgh S (2014) Gout: joints and beyond, epidemiology, clinical features, treatment and co-morbidities. Maturitas 78:245–251CrossRefPubMed Robinson PC, Horsburgh S (2014) Gout: joints and beyond, epidemiology, clinical features, treatment and co-morbidities. Maturitas 78:245–251CrossRefPubMed
2.
go back to reference Otokozawa S, Ai M, Asztalos BF, White CC, Demissie-Banjaw S et al (2010) Direct assessment of plasma low density lipoprotein and high density lipoprotein cholesterol levels and coronary heart disease: results from the Framingham Offspring Study. Atherosclerosis 213:251–255PubMedCentralCrossRefPubMed Otokozawa S, Ai M, Asztalos BF, White CC, Demissie-Banjaw S et al (2010) Direct assessment of plasma low density lipoprotein and high density lipoprotein cholesterol levels and coronary heart disease: results from the Framingham Offspring Study. Atherosclerosis 213:251–255PubMedCentralCrossRefPubMed
3.
go back to reference Gonzalez-Senac NM, Bailen R, Torres RJ, de Miguel E, Puig JG (2014) Metabolic syndrome in primary gout. Nucleosides Nucleotides Nucleic Acids 33:185–191CrossRefPubMed Gonzalez-Senac NM, Bailen R, Torres RJ, de Miguel E, Puig JG (2014) Metabolic syndrome in primary gout. Nucleosides Nucleotides Nucleic Acids 33:185–191CrossRefPubMed
5.
go back to reference George RL, Keenan RT (2013) Genetics of hyperuricemia and gout: implications for the present and future. Curr Rheumatol Rep 15:309CrossRefPubMed George RL, Keenan RT (2013) Genetics of hyperuricemia and gout: implications for the present and future. Curr Rheumatol Rep 15:309CrossRefPubMed
6.
go back to reference Koettgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J et al (2013) Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet 45:145–154CrossRef Koettgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J et al (2013) Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet 45:145–154CrossRef
7.
go back to reference Cervero P, Himmel M, Krueger M, Linder S (2012) Proteomic analysis of podosome fractions from macrophages reveals similarities to spreading initiation centres. Eur J Cell Biol 91:908–922CrossRefPubMed Cervero P, Himmel M, Krueger M, Linder S (2012) Proteomic analysis of podosome fractions from macrophages reveals similarities to spreading initiation centres. Eur J Cell Biol 91:908–922CrossRefPubMed
8.
go back to reference Kile BT, Panopoulos AD, Stirzaker RA, Hacking DF, Tahtamouni LH et al (2007) Mutations in the cofilin partner AIP1/WDR1 cause autoinflammatory disease and macrothrombocytopenia. Blood 110:2371–2380PubMedCentralCrossRefPubMed Kile BT, Panopoulos AD, Stirzaker RA, Hacking DF, Tahtamouni LH et al (2007) Mutations in the cofilin partner AIP1/WDR1 cause autoinflammatory disease and macrothrombocytopenia. Blood 110:2371–2380PubMedCentralCrossRefPubMed
9.
10.
go back to reference Yu J, Riou C, Davidson D, Minhas R, Robson JD et al (2001) Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk and serine/threonine protein kinase HPK-1. Mol Cell Biol 21:6102–6112PubMedCentralCrossRefPubMed Yu J, Riou C, Davidson D, Minhas R, Robson JD et al (2001) Synergistic regulation of immunoreceptor signaling by SLP-76-related adaptor Clnk and serine/threonine protein kinase HPK-1. Mol Cell Biol 21:6102–6112PubMedCentralCrossRefPubMed
11.
go back to reference Wei W-H, Guo Y, Kindt ASD, Merriman TR, Semple CA et al (2014) Abundant local interactions in the 4p16. 1 region suggest functional mechanisms underlying SLC2A9 associations with human serum uric acid. Hum Mol Genet 23:5061–5068PubMedCentralCrossRefPubMed Wei W-H, Guo Y, Kindt ASD, Merriman TR, Semple CA et al (2014) Abundant local interactions in the 4p16. 1 region suggest functional mechanisms underlying SLC2A9 associations with human serum uric acid. Hum Mol Genet 23:5061–5068PubMedCentralCrossRefPubMed
12.
go back to reference Jin TB, Ren YC, Shi XG, Jiri M, He N et al (2015) Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case–control sample sets. Rheumatol Int 35:1141–1147CrossRefPubMed Jin TB, Ren YC, Shi XG, Jiri M, He N et al (2015) Genetic variations in the CLNK gene and ZNF518B gene are associated with gout in case–control sample sets. Rheumatol Int 35:1141–1147CrossRefPubMed
13.
go back to reference Foggin PM, Torrance ME, Dorje D, Xuri W, Marc Foggin J et al (2006) Assessment of the health status and risk factors of Kham Tibetan pastoralists in the alpine grasslands of the Tibetan plateau. Soc Sci Med (1982) 63:2512–2532CrossRef Foggin PM, Torrance ME, Dorje D, Xuri W, Marc Foggin J et al (2006) Assessment of the health status and risk factors of Kham Tibetan pastoralists in the alpine grasslands of the Tibetan plateau. Soc Sci Med (1982) 63:2512–2532CrossRef
14.
go back to reference Malik A, Schumacher HR, Dinnella JE, Clayburne GM (2009) Clinical diagnostic criteria for gout: comparison with the gold standard of synovial fluid crystal analysis. J Clin Rheumatol 15:22–24CrossRefPubMed Malik A, Schumacher HR, Dinnella JE, Clayburne GM (2009) Clinical diagnostic criteria for gout: comparison with the gold standard of synovial fluid crystal analysis. J Clin Rheumatol 15:22–24CrossRefPubMed
15.
go back to reference Gabriel S, Ziaugra L, Tabbaa D (2009) SNP genotyping using the Sequenom MassARRAY iPLEX platform. In: Haines JL et al (eds) Current protocols in human genetics/editorial board, Chapter 2: Unit 2.12–Unit 12.12 Gabriel S, Ziaugra L, Tabbaa D (2009) SNP genotyping using the Sequenom MassARRAY iPLEX platform. In: Haines JL et al (eds) Current protocols in human genetics/editorial board, Chapter 2: Unit 2.12–Unit 12.12
16.
go back to reference Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T et al (2007) High-throughput oncogene mutation profiling in human cancer. Nat Genet 39:347–351CrossRefPubMed Thomas RK, Baker AC, Debiasi RM, Winckler W, Laframboise T et al (2007) High-throughput oncogene mutation profiling in human cancer. Nat Genet 39:347–351CrossRefPubMed
18.
go back to reference Wiedemann E, Rose HG, Schwartz E (1972) Plasma lipoproteins, glucose tolerance and insulin response in primary gout. Am J Med 53:299–307CrossRefPubMed Wiedemann E, Rose HG, Schwartz E (1972) Plasma lipoproteins, glucose tolerance and insulin response in primary gout. Am J Med 53:299–307CrossRefPubMed
19.
go back to reference Padova J, Patchefsky A, Onesti G, Faludi G, Bendersky G (1964) The effect of glucose loads on renal uric acid excretion in diabetic patients. Metabolism 13:507–512CrossRefPubMed Padova J, Patchefsky A, Onesti G, Faludi G, Bendersky G (1964) The effect of glucose loads on renal uric acid excretion in diabetic patients. Metabolism 13:507–512CrossRefPubMed
20.
go back to reference Lipkowitz MS (2012) Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep 14:179–188CrossRefPubMed Lipkowitz MS (2012) Regulation of uric acid excretion by the kidney. Curr Rheumatol Rep 14:179–188CrossRefPubMed
21.
go back to reference Dong J, Yu S, Yang R, Li H, Guo H et al (2014) A simple and precise method for direct measurement of fractional esterification rate of high density lipoprotein cholesterol by high performance liquid chromatography. Clin Chem Lab Med 52:557–564CrossRefPubMed Dong J, Yu S, Yang R, Li H, Guo H et al (2014) A simple and precise method for direct measurement of fractional esterification rate of high density lipoprotein cholesterol by high performance liquid chromatography. Clin Chem Lab Med 52:557–564CrossRefPubMed
22.
go back to reference Fujibuchi T, Abe Y, Takeuchi T, Imai Y, Kamei Y et al (2005) AIP1/WDR1 supports mitotic cell rounding. Biochem Biophys Res Commun 327:268–275CrossRefPubMed Fujibuchi T, Abe Y, Takeuchi T, Imai Y, Kamei Y et al (2005) AIP1/WDR1 supports mitotic cell rounding. Biochem Biophys Res Commun 327:268–275CrossRefPubMed
23.
go back to reference Liu R, Liote F, Rose DM, Merz D, Terkeltaub R (2004) Proline-rich tyrosine kinase 2 and Src kinase signaling transduce monosodium urate crystal-induced nitric oxide production and matrix metalloproteinase 3 expression in chondrocytes. Arthritis Rheum 50:247–258CrossRefPubMed Liu R, Liote F, Rose DM, Merz D, Terkeltaub R (2004) Proline-rich tyrosine kinase 2 and Src kinase signaling transduce monosodium urate crystal-induced nitric oxide production and matrix metalloproteinase 3 expression in chondrocytes. Arthritis Rheum 50:247–258CrossRefPubMed
24.
go back to reference Wang X, Shaw S, Amiri F, Eaton DC, Marrero MB (2002) Inhibition of the Jak/STAT signaling pathway prevents the high glucose-induced increase in TGF-beta and fibronectin synthesis in mesangial cells. Diabetes 51:3505–3509CrossRefPubMed Wang X, Shaw S, Amiri F, Eaton DC, Marrero MB (2002) Inhibition of the Jak/STAT signaling pathway prevents the high glucose-induced increase in TGF-beta and fibronectin synthesis in mesangial cells. Diabetes 51:3505–3509CrossRefPubMed
25.
go back to reference Marrero MB, Banes-Berceli AK, Stern DM, Eaton DC (2006) Role of the JAK/STAT signaling pathway in diabetic nephropathy. Am J Physiol Renal Physiol 290:F762–F768CrossRefPubMed Marrero MB, Banes-Berceli AK, Stern DM, Eaton DC (2006) Role of the JAK/STAT signaling pathway in diabetic nephropathy. Am J Physiol Renal Physiol 290:F762–F768CrossRefPubMed
26.
go back to reference Siniachenko OV, Diadyk AI, Nikolenko IuI, Khomenko MV (1984) Circulating immune complexes in gout. Vrach Delo (9):61–63 Siniachenko OV, Diadyk AI, Nikolenko IuI, Khomenko MV (1984) Circulating immune complexes in gout. Vrach Delo (9):61–63
Metadata
Title
WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients
Authors
Bing Lan
Peng Chen
Mutu Jiri
Na He
Tian Feng
Kai Liu
Tianbo Jin
Longli Kang
Publication date
01-03-2016
Publisher
Springer Berlin Heidelberg
Published in
Rheumatology International / Issue 3/2016
Print ISSN: 0172-8172
Electronic ISSN: 1437-160X
DOI
https://doi.org/10.1007/s00296-015-3378-y

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