Association of JAZF1 and TSPAN8/LGR5 variants in relation to type 2 diabetes mellitus in a Saudi population.
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a chronic and multifactorial disease with a rapidly rising incidence in Saudi Arabia. Various genes including zinc finger protein 1 (JAZF1) and tetraspanin 8/leucine-rich repeat-containing G protein-coupled receptor (TSPAN8/LGR5) have been previously described to be associated with T2DM. This study investigated the association of JAZF1 (rs864745) and TSPAN8 (rs7961581) with T2DM in a Saudi population.


METHODS
Genomic DNA samples from 400 Saudi T2DM patients and 400 healthy controls were genotyped and analyzed using a polymerase chain reaction-restriction fragment length polymorphism method. The difference between the genotype frequencies were carried out with Chi-square test. Odds ratio, 95 % confidence intervals and p values were calculated using multinomial logistic regression. Dominant and recessive models were implemented to show the statistical significances. Analysis of variance was used to compare differences between genotypes for the various parameters.


RESULTS
Distribution frequencies of the AA, AG, and GG genotypes of JAZF1 (rs864745) differed significantly among T2DM patients and healthy controls (p < 0.05). The AG and GG genotypes were independently and significantly associated with a T2DM risk after adjusting for factors such as age, sex, and body mass index [odds ratio (OR) 2.1 (95 % confidence interval (CI) 1.3-3.4); p = 0.002] and [OR 1.9 (95 % CI 1.2-3.1); p = 0.005], respectively. A genotype-based stratification of anthropometric and biochemical data revealed that the AG + GG genotype is associated with waist circumference (p = 0.04) and fasting blood glucose (p = 0.01) and high-density lipoprotein cholesterol levels (p = 0.02). None of the allele or genotype showed the significant association between the T2DM cases and control subjects in rs7961581 polymorphism in TSPAN8/LGR5 gene.


CONCLUSIONS
The rs864745 variant in JAZF1 gene may act as genetic risk factors for the development of T2DM in a Saudi population.
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433 Kingdom of Saudi Arabia.
Khalid Khalaf
KK
Alharbi
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433 Kingdom of Saudi Arabia.
Imran
I
Ali Khan
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, P.O. Box 10219, Riyadh, 11433 Kingdom of Saudi Arabia.
Rabbani
R
Syed
Department of Biology Science, College of Science and Arts, Al-Qassim University, PO Box 1300, Buraidah, 51431 Kingdom of Saudi Arabia.
Fawiziah Khalaf
FK
Alharbi
Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia ; Biomarkers Research Program, Department of Biochemistry, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia.
Abdul Khader
AK
Mohammed
Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia.
Benjamin
B
Vinodson
Prince Mutaib Chair for Biomarkers of Osteoporosis, Biochemistry Department, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia ; Biomarkers Research Program, Department of Biochemistry, College of Science, King Saud University, Riyadh, 11451 Saudi Arabia.
Nasser M
NM
Al-Daghri
JAZF1; Saudi population; T2DM; TSPAN8/LGR5