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Absence of birth-weight lowering effect of ADCY5 and Near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians

Absence of birth-weight lowering effect of ADCY5 and Near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians
Absence of birth-weight lowering effect of ADCY5 and Near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians
Background: A feature of the Asian Indian phenotype is low birth weight with increased adult type 2 diabetes risk. Most populations show consistent associations between low birth weight and adult type 2 diabetes. Recently, two birth weight-lowering loci on chromosome 3 (near CCNL1 and ADCY5) were identified in a genome-wide association study, the latter of which is also a type 2 diabetes locus. We therefore tested the impact of these genetic variants on birth weight and adult glucose/insulin homeostasis in a large Indian birth cohort.

Methodology/Principal Findings: Adults (n = 2,151) enrolled in a birth cohort (established 1969-73) were genotyped for rs900400 (near CCNL1) and rs9883204 (ADCY5). Associations were tested for birth weight, anthropometry from infancy to adulthood, and type 2 diabetes related glycemic traits. The average birth weight in this population was 2.79±0.47 kg and was not associated with genetic variation in CCNL1 (p = 0.87) or ADCY5 (p = 0.54). Allele frequencies for the ‘birth weight-lowering’ variants were similar compared with Western populations. There were no significant associations with growth or adult weight. However, the ‘birth weight-lowering’ variant of ADCY5 was associated with modest increase in fasting glucose (? 0.041, p = 0.027), 2-hours glucose (? 0.127, p = 0.019), and reduced insulinogenic index (? -0.106, p = 0.050) and 2-hour insulin (? -0.058, p = 0.010).

Conclusions: The low birth weight in Asian Indians is not even partly explained by genetic variants near CCNL1 and ADCY5 which implies that non-genetic factors may predominate. However, the ‘birth-weight-lowering’ variant of ADCY5 was associated with elevated glucose and decreased insulin response in early adulthood which argues for a common genetic cause of low birth weight and risk of type 2 diabetes.
1932-6203
e21331
Vasan, Senthil K.
57b46c7b-074d-4d99-a284-40b592aec067
Neville, Matt J.
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Antonisamy, Belavendra
ec356bbb-f468-48a3-a375-ec2f3b20852a
Samuel, Prasanna
1279c574-c106-407d-8c8d-b93f1e93eead
Fall, Caroline H.
7171a105-34f5-4131-89d7-1aa639893b18
Geethanjali, Finney S.
a3e2b129-87f5-40de-bcaf-af4f2e76a500
Thomas, Nihal
c278277e-19ca-43fd-9d42-d9b4d9667001
Raghupathy, Palany
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Brismar, Ker
a200e258-f48a-4c97-8f7a-931157e76438
Karpe, Fredrik
05abcb32-83b7-44eb-ab12-7c360f4f9c12
Vasan, Senthil K.
57b46c7b-074d-4d99-a284-40b592aec067
Neville, Matt J.
1f35a44c-2fd6-4923-a955-e244954fa109
Antonisamy, Belavendra
ec356bbb-f468-48a3-a375-ec2f3b20852a
Samuel, Prasanna
1279c574-c106-407d-8c8d-b93f1e93eead
Fall, Caroline H.
7171a105-34f5-4131-89d7-1aa639893b18
Geethanjali, Finney S.
a3e2b129-87f5-40de-bcaf-af4f2e76a500
Thomas, Nihal
c278277e-19ca-43fd-9d42-d9b4d9667001
Raghupathy, Palany
76cc790f-9c8d-4085-b9d0-27a26a316e40
Brismar, Ker
a200e258-f48a-4c97-8f7a-931157e76438
Karpe, Fredrik
05abcb32-83b7-44eb-ab12-7c360f4f9c12

Vasan, Senthil K., Neville, Matt J., Antonisamy, Belavendra, Samuel, Prasanna, Fall, Caroline H., Geethanjali, Finney S., Thomas, Nihal, Raghupathy, Palany, Brismar, Ker and Karpe, Fredrik (2011) Absence of birth-weight lowering effect of ADCY5 and Near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. PLoS ONE, 6 (6), e21331. (doi:10.1371/journal.pone.0021331). (PMID:21712988)

Record type: Article

Abstract

Background: A feature of the Asian Indian phenotype is low birth weight with increased adult type 2 diabetes risk. Most populations show consistent associations between low birth weight and adult type 2 diabetes. Recently, two birth weight-lowering loci on chromosome 3 (near CCNL1 and ADCY5) were identified in a genome-wide association study, the latter of which is also a type 2 diabetes locus. We therefore tested the impact of these genetic variants on birth weight and adult glucose/insulin homeostasis in a large Indian birth cohort.

Methodology/Principal Findings: Adults (n = 2,151) enrolled in a birth cohort (established 1969-73) were genotyped for rs900400 (near CCNL1) and rs9883204 (ADCY5). Associations were tested for birth weight, anthropometry from infancy to adulthood, and type 2 diabetes related glycemic traits. The average birth weight in this population was 2.79±0.47 kg and was not associated with genetic variation in CCNL1 (p = 0.87) or ADCY5 (p = 0.54). Allele frequencies for the ‘birth weight-lowering’ variants were similar compared with Western populations. There were no significant associations with growth or adult weight. However, the ‘birth weight-lowering’ variant of ADCY5 was associated with modest increase in fasting glucose (? 0.041, p = 0.027), 2-hours glucose (? 0.127, p = 0.019), and reduced insulinogenic index (? -0.106, p = 0.050) and 2-hour insulin (? -0.058, p = 0.010).

Conclusions: The low birth weight in Asian Indians is not even partly explained by genetic variants near CCNL1 and ADCY5 which implies that non-genetic factors may predominate. However, the ‘birth-weight-lowering’ variant of ADCY5 was associated with elevated glucose and decreased insulin response in early adulthood which argues for a common genetic cause of low birth weight and risk of type 2 diabetes.

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Published date: 21 June 2011

Identifiers

Local EPrints ID: 192495
URI: http://eprints.soton.ac.uk/id/eprint/192495
ISSN: 1932-6203
PURE UUID: 31801a27-1026-480d-ba79-c1986ac12bc6
ORCID for Caroline H. Fall: ORCID iD orcid.org/0000-0003-4402-5552

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Date deposited: 05 Jul 2011 08:26
Last modified: 15 Mar 2024 02:39

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Contributors

Author: Senthil K. Vasan
Author: Matt J. Neville
Author: Belavendra Antonisamy
Author: Prasanna Samuel
Author: Finney S. Geethanjali
Author: Nihal Thomas
Author: Palany Raghupathy
Author: Ker Brismar
Author: Fredrik Karpe

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