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 id...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2011
|
| _version_ | 1826265852361572352 |
|---|---|
| author | Vasan, S Neville, M Antonisamy, B Samuel, P Fall, C Geethanjali, F Thomas, N Raghupathy, P Brismar, K Karpe, F |
| author_facet | Vasan, S Neville, M Antonisamy, B Samuel, P Fall, C Geethanjali, F Thomas, N Raghupathy, P Brismar, K Karpe, F |
| author_sort | Vasan, S |
| collection | OXFORD |
| description | 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 (β 0.041, p = 0.027), 2-hours glucose (β 0.127, p = 0.019), and reduced insulinogenic index (β -0.106, p = 0.050) and 2-hour insulin (β -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. |
| first_indexed | 2024-03-06T20:30:07Z |
| format | Journal article |
| id | oxford-uuid:30bfbd48-8d10-44ff-aaf1-cd5e1987b494 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:30:07Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:30bfbd48-8d10-44ff-aaf1-cd5e1987b4942022-03-26T13:03:33ZAbsence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:30bfbd48-8d10-44ff-aaf1-cd5e1987b494EnglishSymplectic Elements at Oxford2011Vasan, SNeville, MAntonisamy, BSamuel, PFall, CGeethanjali, FThomas, NRaghupathy, PBrismar, KKarpe, FBACKGROUND: 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 (β 0.041, p = 0.027), 2-hours glucose (β 0.127, p = 0.019), and reduced insulinogenic index (β -0.106, p = 0.050) and 2-hour insulin (β -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. |
| spellingShingle | Vasan, S Neville, M Antonisamy, B Samuel, P Fall, C Geethanjali, F Thomas, N Raghupathy, P Brismar, K Karpe, F Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. |
| title | Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. |
| title_full | Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. |
| title_fullStr | Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. |
| title_full_unstemmed | Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. |
| title_short | Absence of birth-weight lowering effect of ADCY5 and near CCNL, but association of impaired glucose-insulin homeostasis with ADCY5 in Asian Indians. |
| title_sort | absence of birth weight lowering effect of adcy5 and near ccnl but association of impaired glucose insulin homeostasis with adcy5 in asian indians |
| work_keys_str_mv | AT vasans absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT nevillem absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT antonisamyb absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT samuelp absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT fallc absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT geethanjalif absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT thomasn absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT raghupathyp absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT brismark absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians AT karpef absenceofbirthweightloweringeffectofadcy5andnearccnlbutassociationofimpairedglucoseinsulinhomeostasiswithadcy5inasianindians |