Type 2 Diabetes Risk Allele Loci in the Qatari Population

O’Beirne, Sarah L.; Salit, Jacqueline; Rodríguez-Flores, Juan L.; Staudt, Michelle R.; Khalil, Charbel Abi; Fakhro, Khalid; Robay, Amal; Ramstetter, Monica D.; Al-Azwani, Iman K.; Malek, Joel A.; Zirie, Mahmoud; Jayyousi, Amin; Badii, Ramin; Al‐Marri, Ajayeb Al‐Nabet; Chiuchiolo, Marı́a J.; Al-Shakaki, Alya; Chidiac, Omar; Gharbiah, Maey; Bener, Abdulbari; Stadler, Dora J.; Hackett, Neil R.; Mezey, Jason G.; Crystal, Ronald G.

doi:10.1371/journal.pone.0156834

Cited by 26 publications

(39 citation statements)

References 43 publications

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“…For complex traits and diseases, there are many GWAS loci which could not be replicated across different ethnicities, such as the SNP rs7756992 in the CDKAL1 gene which strongly associates with T2D in subjects of European ancestry, but displayed no association in a population of West Africa ( Steinthorsdottir et al, 2007 ). Among the 37 SNPs associated with T2D in European or Asian populations, only two were replicated in a Qatari population ( O’Beirne et al, 2016 ). In the Jordan subpopulations examined, we observed a significant association of rs6134031 and T2D, with a very large effect size.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations

Dajani

Wei

et al. 2017

PeerJ

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The prevalence of Type II Diabetes (T2D) has been increasing and has become a disease of significant public health burden in Jordan. None of the previous genome-wide association studies (GWAS) have specifically investigated the Middle East populations. The Circassian and Chechen communities in Jordan represent unique populations that are genetically distinct from the Arab population and other populations in the Caucasus. Prevalence of T2D is very high in both the Circassian and Chechen communities in Jordan despite low obesity prevalence. We conducted GWAS on T2D in these two populations and further performed meta-analysis of the results. We identified a novel T2D locus at chr20p12.2 at genome-wide significance (rs6134031, P = 1.12 × 10−8) and we replicated the results in the Wellcome Trust Case Control Consortium (WTCCC) dataset. Another locus at chr12q24.31 is associated with T2D at suggestive significance level (top SNP rs4758690, P = 4.20 × 10−5) and it is a robust eQTL for the gene, MLXIP (P = 1.10 × 10−14), and is significantly associated with methylation level in MLXIP, the functions of which involves cellular glucose response. Therefore, in this first GWAS of T2D in Jordan subpopulations, we identified novel and unique susceptibility loci which may help inform the genetic underpinnings of T2D in other populations.

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Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations

Dajani

Wei

et al. 2017

PeerJ

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“…None the less, as there was no association and the percentage of subjects with diabetes did not differ significantly between the genotypes, all subjects for any given genotype were grouped and compared with the vitamin D levels. Others have looked at the haplotype analysis showing that the Qatari haplotypes in the region of known diabetes risk in the Q1 and Q2 populations did not differ from European haplotypes [3], though exome sequencing has shown risk variants for Mendelian disorders at high prevalence in Qatar due to consanguinity [2]. Males showed higher levels of 25(OH)D, 1,25(OH)2D (p < 0.001), and 24,25(OH)2D, but not of 3epi-25(OH)D. Lower vitamin D concentrations in the Qatari females versus males are also in accord with other studies [33], though this is not a universal finding [27].…”

Section: Discussionmentioning

confidence: 99%

“…e recruitment strategy for the subjects in this study has been described before [3]. Briefly, all subjects were over the age of 30, and there were a minimum of three generations Qatari.…”

Section: Study Populationmentioning

confidence: 99%

“…Briefly, all subjects were over the age of 30, and there were a minimum of three generations Qatari. Cases were excluded if any of the following were present: history of type 1 diabetes, maturity onset diabetes of the young (MODY), maternally inherited diabetes and deafness syndrome (MIDD), a first degree relative with type 1 diabetes, or secondary diabetes [3]. e diagnosis of type 2 diabetes was made according to the WHO guidelines [29]; for inclusion in the type 2 diabetes cohort, at least one of the following was required: fasting plasma glucose >7 mmol/l, HbA1c > 6.5%, or a diagnostic glucose tolerance test.…”

Section: Study Populationmentioning

confidence: 99%

“…Next generation exome sequencing has identified three major genetic subgroups within the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, and Q3 African) and has identified variants within genes that have effects on clinically significant Mendelian diseases [1][2][3]. Several of these Mendelian variants were only segregating in one Qatari subpopulation [2].…”

Section: Introductionmentioning

confidence: 99%

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Association of Differing Qatari Genotypes with Vitamin D Metabolites

Dakroury

Butler

Dargham

et al. 2020

International Journal of Endocrinology

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Objective. Genetic studies have identified four Qatari genotypes: Q1 Arab, Bedouin; Q2 Asian/Persian; Q3 African; and a fourth admixed group not fitting into the previous 3 groups. This study was undertaken to determine if there was an increased risk of deficiency of vitamin D and its metabolites associated with differing genotypes, perhaps due to genetic differences in skin pigmentation. Methods. 398 Qatari subjects (220 type 2 diabetes and 178 controls) had their genotype determined by Affymetrix 500 k SNP arrays. Total values of 1,25-dihydroxyvitamin D (1,25(OH)2D), 25-hydroxyvitamin D (25(OH)D), 24,25-dihydroxyvitamin D (24,25(OH)2D), and 25-hydroxy-3epi-vitamin D (3epi-25(OH)D) concentrations were measured by the LC-MS/MS analysis. Results. The distribution was as follows: 164 (41.2%) genotyped Q1, 149 (37.4%) genotyped Q2, 31 (7.8%) genotyped Q3, and 54 (13.6%) genotyped “admixed.” Median levels of 25(OH)D and 3epi-25(OH)D did not differ across Q1, Q2, Q3, and “admixed” genotypes, respectively. 1,25(OH)2D levels were lower (p<0.04) between Q2 and the admixed groups, and 24,25(OH)2D levels were lower (p<0.05) between Q1 and the admixed groups. Vitamin D metabolite levels were lower in females for 25(OH)D, 1,25(OH)2D (p<0.001), and 24,25(OH)2D (p<0.006), but 3epi-25(OH)D did not differ (p<0.26). Diabetes prevalence was not different between genotypes. Total 1,25(OH)2D (p<0.001), total 24,25(OH)2D (p<0.001), and total 3epi-25(OH)D (p<0.005) were all significantly lower in diabetes patients compared to controls whilst the total 25(OH)D was higher in diabetes than controls (p<0.001). Conclusion. Whilst 25(OH)D levels did not differ between genotype groups, 1,25(OH)2D and 24,25(OH)2D were lower in the admixed group, suggesting that there are genetic differences in vitamin D metabolism that may be of importance in a population that may allow a more targeted approach to vitamin D replacement. This may be of specific importance in vitamin D replacement strategies with the Q2 genotype requiring less, and the other genotypes requiring more to increase 1,25(OH)2D. Whilst overall the group was vitamin D deficient, total 25(OH)D was higher in diabetes, but 1,25(OH)2D, 24,25(OH)2D, and 3epi-25(OH)D were lower in diabetes that did not affect the relationship to genotype.

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Association between type 2 diabetes mellitus & TCF7L2 gene variants in the Emirati population: Genetics of diabetes in the United Arab Emirates

Khan

Karte

Chehadeh

et al. 2020

American J Hum Biol

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Objective Type 2 diabetes mellitus (T2DM) has a multifactorial etiology involving a complex interplay between genes and the environment. The prevalence of T2DM among the countries of the Gulf Corporation Council (GCC), including the United Arab Emirates (UAE), ranks among the top 15 in the world. A number of studies have shown an increase in T2DM risk for the “TT” genotype at the rs4506565 and rs12255372 Single Nucleotide Polymorphisms (SNP) of the TCF7L2 gene. However, the association between TCF7L2 and T2DM still needs to be investigated in the UAE population. Therefore, this study analyzed the potential associations with rs4506565 and rs12255372 in UAE subjects. Methods For this case‐control study, T2DM patients (n = 890) and healthy subjects (n = 686) were genotyped using a Taqman Real‐Time PCR assay. Statistical analysis was performed with the resulting data using the R (version 3.3.1) and STATA (version 13) software packages. Results The rs12255372 SNP was significantly associated with T2DM (OR = 1.16, 95% CI = 1.00‐1.34; P = .042). However, no significant association was found for the rs4506565 SNP (P = .120). After gender stratification, a significant association was found for both SNPs in males (Prs4506565 = .009 and Prs12255372 = .021). Interestingly, we found the interaction between the SNP rs4506565 with gender alone (P = .032) and in conjunction with BMI and age (P = .036) confers associations with T2DM. Conclusions These findings suggest that the genetic variants of the TCF7L2 gene are associated with an increased susceptibility to T2DM, especially in Emirati males. Our study also highlights the impact of biological and environmental risk factors including age, BMI, and gender on the genetic susceptibility to T2DM.

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Type 2 Diabetes Risk Allele Loci in the Qatari Population

Cited by 26 publications

References 43 publications

Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations

Genome-wide association study identifies novel type II diabetes risk loci in Jordan subpopulations

Association of Differing Qatari Genotypes with Vitamin D Metabolites

Association between type 2 diabetes mellitus & TCF7L2 gene variants in the Emirati population: Genetics of diabetes in the United Arab Emirates

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