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Response to Comment on: Lin et al. (2007) SUMO4 M55V Variant Is Associated With Diabetic Nephropathy in Type 2 Diabetes: Diabetes 56:1177–1180

¹ Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
² Graduate Institute of Medical Genetics, Kaohsiung Medical University, Kaohsiung, Taiwan
³ Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Address correspondence to Shyi-Jang Shin, MD, PhD, Division of Endocrinology and Metabolism, Kaohsiung Medical University Hospital, 100 Shih-Chuan 1st Rd, Kaohsiung 80708, Taiwan. E-mail: sjshin{at}kmu.edu.tw

We thank Hamann et al. (1) for their interest in our study (2) and for demonstrating their results. They did not find the SUMO4 M55V variant to be associated with diabetic nephropathy in Caucasian patients with type 1 (n = 237) and type 2 (n = 515) diabetes. Our study had found the SUMO4 M55V variant to be associated with diabetic nephropathy in Taiwanese patients with type 2 diabetes (n = 430). We agree that these differences might be explained by the racial background, e.g., with Asian and Caucasian subjects.

In studies from Asian control populations, the frequencies of SUMO4 AA, AG, and GG are reported to be 50.1, 40.0, and 9.9% in Japan (3); 47.9, 41.6, and 10.5% in Korea (4); 46.4, 45.7, and 7.9% in China (5); and 57.6, 35.6, and 6.8% in Taiwan (n = 323, our unpublished data), respectively. These frequencies were, however, different from Caucasian control populations in the studies of Smyth et al. (24.4, 49.0, and 26.6%) (6) and Wang et al. (25.5, 50.1, and 24.4%) (7). Of note is the significant association of the SUMO4 M55V variant with the development of type 1 diabetes from Asian populations (3–5) in contrast to the lack of association with type 1 diabetes in European Caucasian patients (6). More recently, Noso et al. (8) reported the frequencies of SUMO4 AA, AG, and GG to be 41, 47, and 12% in Japanese patients with type 2 diabetes; in our study of a Taiwanese population, the frequencies of these variants were 48, 44, and 8%, respectively (2). However, Hamann et al. did not report the frequency of SUMO4 AA, AG, or GG in their patients with diabetes.

Humans do not always share the same causes and prevalences of diseases. In some cases, these differences are due to genetic or environmental constitution. Some studies have demonstrated that the prevalence of diabetic nephropathy is higher in Asian patients with diabetes than it is among Caucasian patients with diabetes (9,10). In the study by Hamann et al., diabetic nephropathy was defined as microalbuminuria of more than 20 mg/l in two or three samples of morning urine obtained within 12 months (11). However, we determined the severity of diabetic nephropathy by measuring urinary albumin-to-creatinine ratio for three consecutive urine collections and subdividing the results into: 1) normoalbuminuria, 2) microalbuminuria, and 3) macroalbuminuria. The most important finding in our study was a significant linear trend for the SUMO4 genotype between the macroalbuminuric group and normoalbuminuric group. The mean urinary albumin-to-creatinine ratio was significantly higher in the GG group than it was in the AA and AG groups. However, Hamann et al. (1) showed no difference in the prevalence of diabetic nephropathy in patients with AA in comparison to patients with AG and GG.

In conclusion, these two studies indicate significant genetic heterogeneity in the association of the SUMO4 M55V variant with diabetic nephropathy in type 2 diabetic patients between Asian and Caucasian populations.

Received for publication April 20, 2007 and accepted in revised form April 22, 2007

REFERENCES

1. Rudofsky G Jr, Schlotterer A, Nawroth PP, Bierhaus A, Hamann A: Comment on: Lin et al. (2007) SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes: Diabetes 56:1177–1180. Diabetes 56:e11, 2007. DOI: 10.2337/db07-0237[Free Full Text]
2. Lin HY, Wang CL, Hsiao PJ, Lu YC, Chen SY, Lin KD, Hsin SC, Hsieh MC, Shin SJ: SUMO4 M55V variant is associated with diabetic nephropathy in type 2 diabetes. Diabetes 56:1177–1180, 2007[Abstract/Free Full Text]
3. Noso S, Ikegami H, Fujisawa T, Kawabata Y, Asano K, Hiromine Y, Tsurumaru M, Sugihara S, Lee I, Kawasaki E, Awata T, Ogihara T: Genetic heterogeneity in association of the SUMO4 M55V variant with susceptibility to type 1 diabetes. Diabetes 54:3582–3586, 2005[Abstract/Free Full Text]
4. Park Y, Park S, Kang J, Yang S, Kim D: Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes. Nat Genet 37:112, 2005[Medline]
5. Guo D, Li M, Zhang Y, Yang P, Eckenrode S, Hopkins D, Zheng W, Purohit S, Podolsky RH, Muir A, Wang J, Dong Z, Brusko T, Atkinson M, Pozzilli P, Zeidler A, Raffel LJ, Jacob CO, Park Y, Serrano-Rios M, Larrad MTM, Zhang Z, Garchon HJ, Bach JF, Rotter JI, She JX, Wang CY: A functional variant of SUMO4, a new IB modifier, is associated with type 1 diabetes. Nat Genet 36:837–841, 2004[Medline]
6. Smyth DJ, Howson JM, Lowe CE, Walker NM, Lam AC, Nutland S, Hutchings J, Tuomilehto-Wolf E, Tuomilehto J, Guja C, Ionescu-Tirgoviste C, Undlien DE, Ronningen KS, Savage D, Dunger DB, Twells RC, McAdle WL, Strachan DP, Todd JA: Assessing the validity of the association between the SUMO4 M55V variant and risk of type 1 diabetes. Nat Genet 37:110–111, 2005[Medline]
7. Wang CY, Podolsky R, She JX: Genetic and functional evidence supporting SUMO4 as a type 1 diabetes susceptibility gene. Ann N Y Acad Sci 1079:257–267, 2006[Medline]
8. Noso S, Ikegami H, Fujisawa T, Kawabata Y, Asano K, Hiromine Y, Fukai A, Ogihara T: Association of small ubiquitin-like modifier 4 (SUMO4) variant, located in IDDM5 locus, with type 2 diabetes in the Japanese population. J Clin Endocrinol Metab 92:2358–2362, 2007[Abstract/Free Full Text]
9. Wu AYT, Kong NCT, Leon FA, Pan CY, Tai TY, Yeung VTF, Yoo SJ, Rouillon A, Weir MR, the MicroAlbuminuria Prevalence Investigators: An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the MicroAlbuminuria Prevalence (MAP) Study. Diabetologia 48:17–26, 2005[Medline]
10. Young BA, Maynard C, Boyko EJ: Racial differences in diabetic nephropathy, cardiovascular disease, and mortality in a national population of veterans. Diabetes Care 26:2392–2399, 2003[Abstract/Free Full Text]
11. Rudofsky G Jr, Schlimme M, Schlotterer A, Eynatten M, Reismann P, Tafel J, Grafe I, Morcos M, Nawroth P, Bierhaus A, Hamann A: No association of the 94T/G polymorphism in the adiponectin gene with diabetic complications. Diabetes Obes Metab 7:455–459, 2005[Medline]

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This Article Extract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Shin, S.-J. Articles by Lin, K.-D. Search for Related Content PubMed Articles by Shin, S.-J. Articles by Lin, K.-D. Social Bookmarking                What's this?