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Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs.
J Hum Genet 2009; 54(3):162-8JH

Abstract

A recent meta-analysis on three genome-wide association (GWA) scans identified six loci (NOTCH2, THADA, ADAMTS9, JAZF1, CDC123/CAMKID and TSPAN8/LGRS) highly associated with type II diabetes (T2D) in Caucasians. This investigation seeks to confirm this association with diabetes and related metabolic traits in Khatri Sikh diabetics of North India. We genotyped highly significant variants from each locus in a case-control cohort consisting of 680 T2D cases and 637 normoglycemic (NG) controls. Only CDC123/CAMKID (rs12779790) replicated earlier evidence of association with T2D under a dominant model (odds ratio (OR): 1.27; 95% confidence interval (CI): 1.02-1.57; P=0.031) during initial testing. However, we could not confirm this association using multiple testing corrections. In a multiple linear-regression analysis, the same variant in the CDC123/CAMKID revealed a marked decrease in fasting insulin levels among 'G' (risk) allele carriers independently in NG controls (P=0.030) and in T2D cases (P=0.009), as well as in the combined sample (P=0.003) after adjusting for covariates. Evidence of impaired beta-cell function was also observed among 'G' (risk) allele carriers in T2D cases (P=0.008) and in a combined cohort (P=0.026). Our data could not confirm the role of the remaining variants with risk either for T2D or quantitative phenotypes measuring insulin secretion or insulin resistance. These findings suggest that CDC123/CAMKID could be a major risk factor for the development of T2D in Sikhs by affecting beta-cell function. To our knowledge, this is the first study reporting the role of recently emerging loci in this high-risk population from the South Asian subcontinent.

Authors+Show Affiliations

Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. dharambir-sanghera@ouhsc.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19247373

Citation

Sanghera, Dharambir K., et al. "Testing the Association of Novel Meta-analysis-derived Diabetes Risk Genes With Type II Diabetes and Related Metabolic Traits in Asian Indian Sikhs." Journal of Human Genetics, vol. 54, no. 3, 2009, pp. 162-8.
Sanghera DK, Been L, Ortega L, et al. Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs. J Hum Genet. 2009;54(3):162-8.
Sanghera, D. K., Been, L., Ortega, L., Wander, G. S., Mehra, N. K., Aston, C. E., ... Ralhan, S. (2009). Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs. Journal of Human Genetics, 54(3), pp. 162-8. doi:10.1038/jhg.2009.7.
Sanghera DK, et al. Testing the Association of Novel Meta-analysis-derived Diabetes Risk Genes With Type II Diabetes and Related Metabolic Traits in Asian Indian Sikhs. J Hum Genet. 2009;54(3):162-8. PubMed PMID: 19247373.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Testing the association of novel meta-analysis-derived diabetes risk genes with type II diabetes and related metabolic traits in Asian Indian Sikhs. AU - Sanghera,Dharambir K, AU - Been,Latonya, AU - Ortega,Lyda, AU - Wander,Gurpreet S, AU - Mehra,Narinder K, AU - Aston,Christopher E, AU - Mulvihill,John J, AU - Ralhan,Sarju, Y1 - 2009/02/27/ PY - 2009/2/28/entrez PY - 2009/2/28/pubmed PY - 2010/2/17/medline SP - 162 EP - 8 JF - Journal of human genetics JO - J. Hum. Genet. VL - 54 IS - 3 N2 - A recent meta-analysis on three genome-wide association (GWA) scans identified six loci (NOTCH2, THADA, ADAMTS9, JAZF1, CDC123/CAMKID and TSPAN8/LGRS) highly associated with type II diabetes (T2D) in Caucasians. This investigation seeks to confirm this association with diabetes and related metabolic traits in Khatri Sikh diabetics of North India. We genotyped highly significant variants from each locus in a case-control cohort consisting of 680 T2D cases and 637 normoglycemic (NG) controls. Only CDC123/CAMKID (rs12779790) replicated earlier evidence of association with T2D under a dominant model (odds ratio (OR): 1.27; 95% confidence interval (CI): 1.02-1.57; P=0.031) during initial testing. However, we could not confirm this association using multiple testing corrections. In a multiple linear-regression analysis, the same variant in the CDC123/CAMKID revealed a marked decrease in fasting insulin levels among 'G' (risk) allele carriers independently in NG controls (P=0.030) and in T2D cases (P=0.009), as well as in the combined sample (P=0.003) after adjusting for covariates. Evidence of impaired beta-cell function was also observed among 'G' (risk) allele carriers in T2D cases (P=0.008) and in a combined cohort (P=0.026). Our data could not confirm the role of the remaining variants with risk either for T2D or quantitative phenotypes measuring insulin secretion or insulin resistance. These findings suggest that CDC123/CAMKID could be a major risk factor for the development of T2D in Sikhs by affecting beta-cell function. To our knowledge, this is the first study reporting the role of recently emerging loci in this high-risk population from the South Asian subcontinent. SN - 1435-232X UR - https://www.unboundmedicine.com/medline/citation/19247373/Testing_the_association_of_novel_meta_analysis_derived_diabetes_risk_genes_with_type_II_diabetes_and_related_metabolic_traits_in_Asian_Indian_Sikhs_ L2 - http://www.diseaseinfosearch.org/result/2236 DB - PRIME DP - Unbound Medicine ER -