Association of the Genetic Polymorphisms in Transcription Factor 7-Like 2 and Peroxisome Proliferator-Activated Receptors- γ 2 with Type 2 Diabetes Mellitus and is Interaction with Obesity Status in Emirati Population.
BACKGROUND
Transcription factor 7-like 2 gene (TCF7L2) and peroxisome proliferator-activated receptors-γ2 (PPAR-γ2) have a profound effect on the incidence of type 2 diabetes mellitus (T2DM) and had previously been found to be associated with T2DM risk in various ppopulations. However, studies in the Arab population are inconsistent. We conducted a case control study to confirm the association of variants rs10885409 of TCF7L2 and Pro12Ala (rs1801282) of PPAR-γ2 with risk of T2DM and related complications in Emirati population of Arab origin. We also investigated the interaction of these associations with obesity status.


METHODS
DNA was extracted from the saliva samples of 272 T2DM patients and 216 nondiabetic Emiratis. Genotyping for rs10885409 (TCF7L2) and rs1801282 (PPAR-γ2 P12A) variants was accomplished with a TaqMan assay. The subgroups were constituted according to obesity status.


RESULTS
In the nonobese group, the rs10885409 C allele in the recessive model was significantly associated with the incidence of T2DM (OR 1.975 [95% CI 1.127-3.461], P = 0.017), but this association was not observed in the obese group or when BMI was not considered. PPAR-γ2 risk allele Pro12 frequency (0.96) was similar in the groups tested and more than 90% population was homozygous for this allele.


CONCLUSIONS
Our case-control study is the first of its kind in Emiratis which establishes TCF7L2 rs10885409 C allele as a T2DM risk factor in Emiratis and this association is modulated by obesity status. We also confirmed that Pro12Ala mutation in PPAR-γ2 is not associated with T2DM risk in this population.
Department of Biomedical Engineering, Khalifa University of Science, Technology & Research, P.O. Box 127788, Abu Dhabi, UAE.
Habiba
H
Al-Safar
Dubai Diabetes Centre, Dubai Health Authority, Dubai, UAE.
Ahmed
A
Hassoun
Department of Biomedical Engineering, Khalifa University of Science, Technology & Research, P.O. Box 127788, Abu Dhabi, UAE.
Shaikha
S
Almazrouei
School of Life Sciences, Manipal University, P.O. Box 345050, Dubai, UAE.
Wala
W
Kamal
Diabetes Clinics, Tawam Hospital, Al-Ain, UAE.
Bachar
B
Afandi
School of Life Sciences, Manipal University, P.O. Box 345050, Dubai, UAE.
Naushad
N
Rais
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000097:blood / Q000208:ethnology / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D014644:Genetic Variation; D005838:Genotype; D064368:Healthy Volunteers; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009765:Obesity / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D047495:PPAR gamma / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*; D014479:United Arab Emirates
D047495:PPAR gamma; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein