Universität zu Köln

Pfister, Roman, Sharp, Stephen, Luben, Robert, Welsh, Paul ORCID: 0000-0002-7970-3643, Barroso, Ines ORCID: 0000-0001-5800-4520, Salomaa, Veikko, Meirhaeghe, Aline ORCID: 0000-0001-6983-2364, Khaw, Kay-Tee, Sattar, Naveed, Langenberg, Claudia ORCID: 0000-0002-5017-7344 and Wareham, Nicholas J. (2011). Mendelian Randomization Study of B-Type Natriuretic Peptide and Type 2 Diabetes: Evidence of Causal Association from Population Studies. PLos Med., 8 (10). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1549-1676

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Abstract

Background: Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded. Methods and Findings: We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders. Conclusions: Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pfister, Roman UNSPECIFIED UNSPECIFIED UNSPECIFIED Sharp, Stephen UNSPECIFIED UNSPECIFIED UNSPECIFIED Luben, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Welsh, Paul UNSPECIFIED orcid.org/0000-0002-7970-3643 UNSPECIFIED Barroso, Ines UNSPECIFIED orcid.org/0000-0001-5800-4520 UNSPECIFIED Salomaa, Veikko UNSPECIFIED UNSPECIFIED UNSPECIFIED Meirhaeghe, Aline UNSPECIFIED orcid.org/0000-0001-6983-2364 UNSPECIFIED Khaw, Kay-Tee UNSPECIFIED UNSPECIFIED UNSPECIFIED Sattar, Naveed UNSPECIFIED UNSPECIFIED UNSPECIFIED Langenberg, Claudia UNSPECIFIED orcid.org/0000-0002-5017-7344 UNSPECIFIED Wareham, Nicholas J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-488595
DOI:	10.1371/journal.pmed.1001112
Journal or Publication Title:	PLos Med.
Volume:	8
Number:	10
Date:	2011
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1549-1676
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HEART-FAILURE; EPIC-NORFOLK; MORTALITY; RISK; GENE; PATHWAY; INSULIN; OBESITY; CANCER; MEN Multiple languages Medicine, General & Internal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48859