Novel Susceptibility Locus at 22q11 for Diabetic Nephropathy in Type 1 Diabetes

[en] Background: Diabetic nephropathy (DN) affects about 30% of patients with type 1 diabetes (T1D) and contributes to serious morbidity and mortality. So far only the 3q21–q25 region has repeatedly been indicated as a susceptibility region for DN. The aim of this study was to search for new DN susceptibility loci in Finnish, Danish and French T1D families. Methods and Results: We performed a genome-wide linkage study using 384 microsatellite markers. A total of 175 T1D families were studied, of which 94 originated from Finland, 46 from Denmark and 35 from France. The whole sample set consisted of 556 individuals including 42 sib-pairs concordant and 84 sib-pairs discordant for DN. Two-point and multi-point non-parametric linkage analyses were performed using the Analyze package and the MERLIN software. A novel DN locus on 22q11 was identified in the joint analysis of the Finnish, Danish and French families by genome-wide multipoint nonparametric linkage analysis using the Kong and Cox linear model (NPLpairs LOD score 3.58). Nominal or suggestive evidence of linkage to this locus was also detected when the three populations were analyzed separately. Suggestive evidence of linkage was found to six additional loci in the Finnish and French sample sets. Conclusions: This study identified a novel DN locus at chromosome 22q11 with significant evidence of linkage to DN. Our results suggest that this locus may be of importance in European populations. In addition, this study supports previously indicated DN loci on 3q21–q25 and 19q13.

Disciplines :

Endocrinology, metabolism & nutrition

Author, co-author :

Wessman, Maija

Forsblom, Carol

Kaunisto, Mari A

So derlund, Jenny

Ilonen, Jorma

Sallinen, Riitta

Hiekkalinna, Tero

Parkkonen, Maija

Maxwell, Alexander P

Tarnow, Lise

More authors (6 more)

Language :

English

Title :

Novel Susceptibility Locus at 22q11 for Diabetic Nephropathy in Type 1 Diabetes

Publication date :

2011

Journal title :

PLoS ONE

eISSN :

1932-6203

Publisher :

Public Library of Science, San Franscisco, United States - California

Volume :

Issue :

Pages :

e24053

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164698/pdf/pone.0024053.pdf

Available on ORBi :

since 16 January 2012

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Bibliography

Andersen AR, Christiansen JS, Andersen JK, Kreiner S, Deckert T, (1983) Diabetic nephropathy in Type 1 (insulin-dependent) diabetes: an epidemiological study. Diabetologia 25: 496-501.
Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR, (1985) The changing natural history of nephropathy in type I diabetes. Am J Med 78: 785-794.
Seaquist ER, Goetz FC, Rich SS, Barbosa J, (1989) Familial clustering of diabetic kidney disease. Evidence for genetic susceptibility to diabetic nephropathy. N Engl J Med 320: 1161-1165.
Borch-Johnsen K, Nörgaard K, Hommel E, Mathiesen ER, Jensen JS, et al. (1992) Is diabetic nephropathy an inherited complication? Kidney Int 41: 719-722.
Quinn M, Angelico MC, Warram JH, Krolewski AS, (1996) Familial factors determine the development of diabetic nephropathy in patients with IDDM. Diabetologia 39: 940-945.
Harjutsalo V, Katoh S, Sarti C, Tajima N, Tuomilehto J, (2004) Population-based assessment of familial clustering of diabetic nephropathy in type 1 diabetes. Diabetes 53: 2449-2454.
Moczulski D, Rogus J, Antonellis A, Warram J, Krolewski A, (1998) Major susceptibility locus for nephropathy in type 1 diabetes on chromosome 3q: results of novel discordant sib-pair analysis. Diabetes 47: 1164-1169.
Rogus JJ, Poznik GD, Pezzolesi MG, Smiles AM, Dunn J, et al. (2008) High-density single nucleotide polymorphism genome-wide linkage scan for susceptibility genes for diabetic nephropathy in type 1 diabetes: discordant sibpair approach. Diabetes 57: 2519-2526.
Osterholm AM, He B, Pitkaniemi J, Albinsson L, Berg T, et al. (2007) Genome-wide scan for type 1 diabetic nephropathy in the Finnish population reveals suggestive linkage to a single locus on chromosome 3q. Kidney Int 71: 140-145.
Chistiakov DA, Savost'anov KV, Shestakova MV, Chugunova LA, Samkhalova MS, et al. (2004) Confirmation of a susceptibility locus for diabetic nephropathy on chromosome 3q23-q24 by association study in Russian type 1 diabetic patients. Diabetes Res Clin Pract 66: 79-86.
He B, Osterholm AM, Hoverfalt A, Forsblom C, Hjorleifsdottir EE, et al. (2009) Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus. Am J Hum Genet 84: 5-13.
Freedman BI, Bostrom M, Daeihagh P, Bowden DW, (2007) Genetic factors in diabetic nephropathy. Clin J Am Soc Nephrol 2: 1306-1316.
Maeda S, (2008) Genetics of diabetic nephropathy. Ther Adv Cardiovasc Dis 2: 363-371.
Pezzolesi MG, Poznik GD, Mychaleckyj JC, Paterson AD, Barati MT, et al. (2009) Genome-wide Association Scan for Diabetic Nephropathy Susceptibility Genes in Type 1 Diabetes Mellitus. Diabetes 58: 1403-1410.
Saraheimo M, Forsblom C, Thorn L, Waden J, Rosengard-Barlund M, et al. (2008) Serum adiponectin and progression of diabetic nephropathy in patients with type 1 diabetes. Diabetes Care 31: 1165-1169.
Hadjadj S, Pean F, Gallois Y, Passa P, Aubert R, et al. (2004) Different patterns of insulin resistance in relatives of type 1 diabetic patients with retinopathy or nephropathy: the Genesis France-Belgium Study. Diabetes Care 27: 2661-2668.
Anttila V, Nyholt DR, Kallela M, Artto V, Vepsalainen S, et al. (2008) Consistently replicating locus linked to migraine on 10q22-q23. Am J Hum Genet 82: 1051-1063.
O'Connell JR, Weeks DE, (1998) PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 63: 259-266.
Hermann R, Turpeinen H, Laine AP, Veijola R, Knip M, et al. (2003) HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families. Tissue Antigens 62: 162-169.
Hiekkalinna T, Terwilliger JD, Sammalisto S, Peltonen L, Perola M, (2005) AUTOGSCAN: powerful tools for automated genome-wide linkage and linkage disequilibrium analysis. Twin Res Hum Genet 8: 16-21.
Abecasis GR, Cherny SS, Cookson WO, Cardon LR, (2002) Merlin-rapid analysis of dense genetic maps using sparse gene flow trees.[see comment]. Nat Genet 30: 97-101.
Vandenplas S, Wiid I, Grobler-Rabie A, Brebner K, Ricketts M, et al. (1984) Blot hybridization analyses of genomic DNA. Journal of Medical Genetics 21: 164-172.
Nyholt DR, Morley KI, Ferreira MA, Medland SE, Boomsma DI, et al. (2005) Genomewide significant linkage to migrainous headache on chromosome 5q21. Am J Hum Genet 77: 500-512.
Kong A, Cox NJ, (1997) Allele-sharing models: LOD scores and accurate linkage tests. Am J Hum Genet 61: 1179-1188.
Feingold E, Brown PO, Siegmund D, (1993) Gaussian models for genetic linkage analysis using complete high-resolution maps of identity by descent. Am J of Hum Genet 53: 234-251.
Lander E, Kruglyak L, (1995) Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet 11: 241-247.
Abecasis GR, Burt RA, Hall D, Bochum S, Doheny KF, et al. (2004) Genomewide scan in families with schizophrenia from the founder population of Afrikaners reveals evidence for linkage and uniparental disomy on chromosome 1. Am J Hum Genet 74: 403-417.
Wiltshire S, Cardon LR, McCarthy MI, (2002) Evaluating the results of genomewide linkage scans of complex traits by locus counting. Am J Hum Genet 71: 1175-1182.
Pociot F, Akolkar B, Concannon P, Erlich HA, Julier C, et al. (2010) Genetics of type 1 diabetes: what's next? Diabetes 59: 1561-1571.
Tuomilehto J, Karvonen M, Pitkaniemi J, Virtala E, Kohtamaki K, et al. (1999) Record-high incidence of Type I (insulin-dependent) diabetes mellitus in Finnish children. The Finnish Childhood Type I Diabetes Registry Group. Diabetologia 42: 655-660.
Igo RP Jr, Iyengar SK, Nicholas SB, Goddard KA, Langefeld CD, et al. (2011) Genomewide Linkage Scan for Diabetic Renal Failure and Albuminuria: The FIND Study. Am J Nephrol 33: 381-389.
Kao WHL, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, et al. (2008) MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 40: 1185.
Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, et al. (2008) MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet 40: 1175-1184.
Tzur S, Rosset S, Shemer R, Yudkovsky G, Selig S, et al. (2010) Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet 128: 345-350.
Gaffen SL, (2009) The role of interleukin-17 in the pathogenesis of rheumatoid arthritis. Curr Rheumatol Rep 11: 365-370.
Navarro-Gonzalez JF, Mora-Fernandez C, de Fuentes MM, Garcia-Perez J, (2011) Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol 7: 327-340.
Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH, (2003) Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients. Diabetologia 46: 1402-1407.
Palmieri F, (2004) The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch 447: 689-709.
Tanaka N, Babazono T, Saito S, Sekine A, Tsunoda T, et al. (2003) Association of Solute Carrier Family 12 (Sodium/Chloride) Member 3 With Diabetic Nephropathy, Identified by Genome-Wide Analyses of Single Nucleotide Polymorphisms. Diabetes 52: 2848-2853.
Kim JH, Shin HD, Park BL, Moon MK, Cho YM, et al. (2006) SLC12A3 (Solute Carrier Family 12 Member [Sodium/Chloride] 3) Polymorphisms Are Associated With End-Stage Renal Disease in Diabetic Nephropathy. Diabetes 55: 843-848.
Akkina S, Becker BN, (2011) MicroRNAs in kidney function and disease. Transl Res 157: 236-240.
Huang B, Starostik P, Kuhl J, Tonn JC, Roggendorf W, (2002) Loss of heterozygosity on chromosome 22 in human ependymomas. Acta Neuropathol 103: 415-420.
McDermid HE, Morrow BE, (2002) Genomic disorders on 22q11. Am J Hum Genet 70: 1077-1088.
Zhang F, Gu W, Hurles ME, Lupski JR, (2009) Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet 10: 451-481.
Kang HS, ZeRuth G, Lichti-Kaiser K, Vasanth S, Yin Z, et al. (2010) Gli-similar (Glis) Kruppel-like zinc finger proteins: insights into their physiological functions and critical roles in neonatal diabetes and cystic renal disease. Histol Histopathol 25: 1481-1496.
Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, et al. (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316: 1341-1345.
Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, et al. (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316: 1336-1341.
Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, et al. (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316: 1491-1493.
Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, et al. (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357: 443-453.
McDonough CW, Palmer ND, Hicks PJ, Roh BH, An SS, et al. (2011) A genome-wide association study for diabetic nephropathy genes in African Americans. Kidney Int 79: 563-572.
Bowden DW, Colicigno CJ, Langefeld CD, Sale MM, Williams A, et al. (2004) A genome scan for diabetic nephropathy in African Americans. Kidney Int 66: 1517-1526.
McKnight AJ, Maxwell AP, Sawcer S, Compston A, Setakis E, et al. (2006) A Genome-Wide DNA Microsatellite Association Screen to Identify Chromosomal Regions Harboring Candidate Genes in Diabetic Nephropathy. J Am Soc Nephrol 17: 831-836.