American Journal of Kidney Diseases
Volume 49, Issue 3 , Pages 394-400, March 2007

A Genome-Wide Search for Linkage to Renal Function Phenotypes in West Africans With Type 2 Diabetes

  • Guanjie Chen, MD

      Affiliations

    • National Human Genome Center at Howard University, College of Medicine, Washington, DC
    • Corresponding Author InformationAddress reprint requests to Guanjie Chen, MD, National Human Genome Center, Howard University, Genetic Epidemiology Unit, College of Medicine, 2216 6th St NW, Washington, DC 20059.
    • ,
  • Adebowale A. Adeyemo, MD

      Affiliations

    • National Human Genome Center at Howard University, College of Medicine, Washington, DC
    • University of Ibadan, College of Medicine, Ibadan
    • ,
  • Jie Zhou, BS

      Affiliations

    • National Human Genome Center at Howard University, College of Medicine, Washington, DC
    • ,
  • Yuanxiu Chen, MD, PhD

      Affiliations

    • National Human Genome Center at Howard University, College of Medicine, Washington, DC
    • ,
  • Ayo Doumatey, MS

      Affiliations

    • National Human Genome Center at Howard University, College of Medicine, Washington, DC
    • ,
  • Kerrie Lashley, BS

      Affiliations

    • National Human Genome Center at Howard University, College of Medicine, Washington, DC
    • ,
  • Hanxia Huang, MD

      Affiliations

    • National Human Genome Center at Howard University, College of Medicine, Washington, DC
    • ,
  • Albert Amoah, MD, PhD

      Affiliations

    • Department of Medicine, University of Ghana Medical School, Accra
    • ,
  • Kofi Agyenim-Boateng, MD

      Affiliations

    • Department of Medicine, University of Science and Technology, Kumasi, Ghana
    • ,
  • Benjamin A. Eghan Jr, MD

      Affiliations

    • Department of Medicine, University of Science and Technology, Kumasi, Ghana
    • ,
  • Godfrey Okafor, MD

      Affiliations

    • Department of Medicine, University of Nigeria Teaching Hospital, Enugu
    • ,
  • Joseph Acheampong, MD

      Affiliations

    • Department of Medicine, University of Science and Technology, Kumasi, Ghana
    • ,
  • Johnnie Oli, MD

      Affiliations

    • Department of Medicine, University of Nigeria Teaching Hospital, Enugu
    • ,
  • Olufemi Fasanmade, MD

      Affiliations

    • Endocrine and Metabolic Unit, University of Lagos, College of Medicine, Lagos, Nigeria.
    • ,
  • Thomas Johnson, MD

      Affiliations

    • Endocrine and Metabolic Unit, University of Lagos, College of Medicine, Lagos, Nigeria.
    • ,
  • Charles Rotimi, PhD

      Affiliations

    • National Human Genome Center at Howard University, College of Medicine, Washington, DC

Received 16 March 2006; accepted 11 December 2006. published online 03 February 2007.

Background

Reduced renal function often is a major consequence of diabetes and hypertension. Although several indices of renal function (eg, creatinine clearance) are clearly heritable and show linkage to several genomic regions, the specific underlying genetic determinants are still being sought. The purpose of this study is to conduct a genome-wide search for regions linked to 3 renal function phenotypes, serum creatinine, creatinine clearance, and glomerular filtration rate (GFR), in persons with type 2 diabetes.

Methods

A genome-wide panel of 372 autosomal short tandem repeat markers at an average spacing of 9 centimorgan were typed in 691 patients with type 2 diabetes (321 sib pairs and 36 half-sib pairs) in an affected sib pair study in West Africa. Linkage analysis was conducted with the 3 phenotypes by using a multipoint variance components linkage method.

Results

Creatinine clearance showed higher logarithm of odds (LOD) score than the other 2 phenotypes. Linkage to creatinine clearance was observed on chromosomes 16 (marker D16S539, LOD score of 3.56, empirical P = 0.0001), 17 (D17S1298, LOD score of 2.08, empirical P = 0.0018), and 7 (D7S1818, LOD score of 1.84, nominal P = 0.00181, empirical P = 0.0022). Maximum LOD scores for serum creatinine were observed on chromosomes 10 (D10S1432, LOD score of 2.53, empirical P = 0.0001) and 3 (D3S2418, LOD score of 2.21, empirical P = 0.0003) and for GFR on chromosomes 6 (D6S1040, LOD score of 2.08, empirical P = 0.0001) and 8 (D8S256, LOD score of 1.80, empirical P = 0.0001). Several of these results are replications of significant findings from other genome scans.

Conclusion

A genome-wide scan for serum creatinine, creatinine clearance, and GFR in a West African sample showed linkage regions that may harbor genes influencing variation in these phenotypes. Potential candidate genes in these regions that have been implicated in diabetic nephropathy and/or renal damage in models of hypertension include CYBA (or P22PHOX) (16q24), NOX1 (10q22), and NOX3 (6q25.1-q26).

Index Words: Renal function, genome scan, type 2 diabetes, West Africa

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 Originally published online as doi:10.1053/j.ajkd.2006.12.011 on February 1, 2007.

 Support: Support for the Africa America Diabetes Mellitus (AADM) study is provided by NIH grant no. 3T37TW00041-03S2 from the Office of Research on Minority Health. This project also is supported in part by the National Center for Research Resources (NCRR), National Human Genome Research Institute (NHGRI), and by the NIDDK grant DK-54001. Genotyping services were provided by the Center for Inherited Disease Research (http://www.cidr.jhmi.edu). The Center for Inherited Disease Research is fully funded through a federal contract from the NIH to Johns Hopkins University, Contract No. N01-HG-65403. Potential conflicts of interest: None.

PII: S0272-6386(06)01912-3

doi:10.1053/j.ajkd.2006.12.011

American Journal of Kidney Diseases
Volume 49, Issue 3 , Pages 394-400, March 2007

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