Genetic association of ITPR3 SNP rs999943 with Type 2 Diabetes and related metabolic traits

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Abstract

Background Prevalence of diabetes has markedly increased over the past three decades in Kuwait with approximately one quarter of its population suffering from Type 2 diabetes (T2D). A combination of genetic and environmental factors impacted by regions socioeconomic status have been widely associated with the onset of the disease. Genetic predisposition to T2D has been proved by monozygotic twin and case control association studies. ITPR3 plays a prominent role in intracellular calcium signaling influencing wide range of cellular and metabolic activities. Aim to explore the genetic association and contribution of ITPR3 SNP rs999943 with the development of T2D and related 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 was carried out using the TaqMan® SNP Genotyping assay on ABI PRISM 7500 Real-Time PCR System. Statistical analysis was carried out using SNPassoc and Genetics software package. Results Screening region of interest revealed significant association of rs999943 A/G SNP with susceptibility to T2D. The frequency of the G allele was higher in T2D subjects (0.30) than that in non-diabetic (0.17), with an OR of 2.02 at 95% CI 1.27-3.18 for the G allele. Heterozygous AG genotype conferred susceptibility to T2D with an OR of 2.13 at 95% CI 1.17-3.39. Stratified analysis of rs999943 SNP revealed significant association of -AG genotype with BMI (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 HDL levels and systolic blood pressure (r2 = 0.30 and p = 0.039. Likewise, a negative correlation was also observed between HDL levels and diastolic blood pressure (r2 = 0.31 and p = 0.009) in individuals carrying rs999413-AG and -GG genotypes. Interestingly, a gender based quantitative trait analysis indicates the significance of ITPR3 rs999943 SNP as a strong genetic determinant of type 2 diabetes and its related metabolic trait in Kuwait women. Analysis indicates a 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 the gender based overriding effect of rs999413 SNP with extreme metabolic phenotypes, driving towards in-depth population based representative studies.
Original languageEnglish
Title of host publicationInternational Diabetes Federation 2017 Congress
Publication statusPublished - 16 Nov 2017
EventInternational Diabetes Federation - Abudhabi , Abudhabi , United Arab Emirates
Duration: 4 Dec 20178 Dec 2017
Conference number: 23

Conference

ConferenceInternational Diabetes Federation
Abbreviated titleIDF
CountryUnited Arab Emirates
CityAbudhabi
Period4/12/178/12/17

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