Identification of Genetic Variants of Gestational Diabetes in South Indians.
BACKGROUND
This study examined the association in a South Indian population with gestational diabetes mellitus (GDM) of type 2 diabetes risk variants that have previously conferred susceptibility to GDM in other populations.


METHODS
The study groups comprised 518 women with GDM and 910 pregnant women with normal glucose tolerance (NGT). Women with GDM were recruited from a tertiary diabetes center in Chennai, in south India, and NGT women were selected from antenatal clinics also in Chennai. Genomic DNA was isolated from whole blood using the phenol chloroform method. Twelve previously reported GDM-associated single nucleotide polymorphisms (SNPs) in or near nine loci were genotyped using the MassARRAY™ system (Sequenom, San Diego, CA).


RESULTS
Among the 12 SNPs genotyped, 11 SNPs were in Hardy-Weinberg equilibrium and had a call rate of >95%. Of the 11 SNPs previously associated with GDM in other populations, significant association was observed only with the rs7754840 and rs7756992 SNPs of the CDK5 regulatory subunit associated protein 1-like 1 (CDKAL1) gene in this population. The minor alleles of the SNPs rs7754840 and rs7756992 showed significant susceptibility to GDM with an odds ratio of 1.34 (95% confidence interval, 1.12-1.60; P = 0.0013) and 1.45 (95% confidence interval, 1.21-1.72; P = 0.00004), respectively.


CONCLUSIONS
The rs7754840 and rs7756992 SNPs of the CDKAL1 gene were found to be associated with GDM in this south Indian population. This is the first study describing genetic susceptibility of GDM in Asian Indians.
1 Madras Diabetes Research Foundation , Chennai, India .
Sekar
S
Kanthimathi
1 Madras Diabetes Research Foundation , Chennai, India .
Manickam
M
Chidambaram
1 Madras Diabetes Research Foundation , Chennai, India .
Samuel
S
Liju
1 Madras Diabetes Research Foundation , Chennai, India .
Balaji
B
Bhavadharini
1 Madras Diabetes Research Foundation , Chennai, India .
Dhanasekaran
D
Bodhini
1 Madras Diabetes Research Foundation , Chennai, India .
Visvanathan Gnana
VG
Prakash
1 Madras Diabetes Research Foundation , Chennai, India .
Anandakumar
A
Amutha
3 SRC Diabetes Care Centre , Erode, India .
Aruyerchelvan
A
Bhavatharini
1 Madras Diabetes Research Foundation , Chennai, India .|2 Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention & Control, IDF Centre of Education , Chennai, India .
Ranjit Mohan
RM
Anjana
1 Madras Diabetes Research Foundation , Chennai, India .|2 Dr. Mohan's Diabetes Specialities Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention & Control, IDF Centre of Education , Chennai, India .
Viswanathan
V
Mohan
1 Madras Diabetes Research Foundation , Chennai, India .
Venkatesan
V
Radha
D000328:Adult; D000483:Alleles; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics; D016640:Diabetes, Gestational / Q000097:blood / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007194:India / Q000208:ethnology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D012307:Risk Factors; D012359:tRNA Methyltransferases
D012359:tRNA Methyltransferases; D051360:Cyclin-Dependent Kinase 5; C525110:CDKAL1 protein, human