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Maisa
Mahmoud Kamkar1*, Sriraman Devarajan2, Aditi Mathur2,
Ajmal Dalwai3, Sameer Hassan4
1Genetics
& Genomics Unit, Biomedical Research Department, Dasman Diabetes Institute,
Kuwait
2Dasman
Diabetes Biobank, Tissue Bank Facility, Dasman Diabetes Institute, Kuwait
3Member
of Australia Institute of Medical Scientists, Australia
4University
of Gothenburg, Sweden
Corresponding
Author: Maisa Mahmoud Kamkar, PhD, Genetics & Genomics Unit,
Biomedical Research Department, Dasman DiabetesInstitute, P.O. Box 1180, Dasman
15462, Kuwait. Emails: maisa.mahmoud@dasmaninstitute.org
or maisa.mkamkar@gmail.com
Citation: Maisa
Mahmoud Kamkar (2020) Potential Genetic Association of ITPR3 SNP rs999943 with
Type 2 Diabetes in Kuwait: Case-Control Pilot Study. Global
Diabetes Open Access Journal, 2(2); 1-3
Copyright: ©
2020, Kamkar MM, et al. This is an open-access article distributed under the
terms of the Creative Commons Attribution 4.0 International License, which
permits unrestricted use, distribution and reproduction in any medium, provided
the original author and source are credited.
ABSTRACT
Background:
Prevalence of diabetes has markedly increased over the past three decades in
Kuwait withapproximately one quarter of its population suffering from Type 2
diabetes (T2D). A combination of genetic andenvironmental factors impacted by
regions socioeconomic status have been widely associated with the onset of
thedisease. Genetic predisposition to T2D has been proved by monozygotic twin
and case control association studies.ITPR3 plays a prominent role in
intracellular calcium signalling influencing wide range of cellular and
metabolicactivities.Aim: to explore
the genetic association and contribution of ITPR3 SNP rs999943 with the
development of T2D andrelated metabolic traits such as body mass index (BMI),
plasma glucose (PG), low density lipoprotein (LDL),triglyceride (TGL), high
density lipoprotein (HDL), total cholesterol (TC), systolic and diastolic blood
pressure(SBP/DBP) in Kuwaiti population.Method:
A subset of 223 Kuwaiti natives (120 T2D and 103 non-diabetic) from a large
cohort collected for genome-wide association study on obesity traits were
included in this study. Genotyping of ITPR3 A/G SNP rs999413 wascarried out
using the TaqMan® SNP Genotyping assay on ABI PRISM 7500 Real-Time PCR System.
Statisticalanalysis was carried out using SNPassoc and Genetics software
package.Results: Screening region of
interest revealed significant association of rs999943 A/G SNP with
susceptibility toT2D. The frequency of the G allele was higher in T2D subjects
(0.30) than that in non-diabetic (0.17), with an OR of2.02 at 95% CI 1.27-3.18
for the G allele. Heterozygous AG genotype conferred susceptibility to T2D with
an OR of2.13 at 95% CI 1.17-3.39. Stratified analysis of rs999943 SNP revealed
significant association of -AG genotype withBMI (p = 0.004), T.CHOL (p =
0.0009), LDL (p = 0.003), TGL (p = 0.005), AHDL (p = 0.0042), SBP (p =
0.0024)and DBP (p = 0.0035). Individuals carrying rs999413-AG genotype, showed
a negative correlation between HDLlevels and systolic blood pressure (r2 = 0.30
and p = 0.039. Likewise, a negative correlation was also observed betweenHDL
levels and diastolic blood pressure (r2 = 0.31 and p = 0.009) in individuals
carrying rs999413-AG and –GGgenotypes. Interestingly, a gender based
quantitative trait analysis indicates the significance of ITPR3 rs999943 SNPas
a strong genetic determinant of type 2 diabetes and its related metabolic trait
in Kuwait women. Analysis indicatesa very strong association of rs999413 SNP
with BMI, total cholesterol, LDL, triglyceride, AHDL, SBP, DBP and cholesterol
in females by all three tested models (p <0.001). Discussion: Our finding indicates significance of rs999413 SNP in
T2D among Kuwaiti natives and highlights thegender based overriding effect of
rs999413 SNP with extreme metabolic phenotypes, driving towards
in-depthpopulation based representative studies.
KEYWORDS:
SNP polymorphism, Genetic Association, SNP Genotyping, T2D
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