Replication study of common variants in CDKAL1 and CDKN2A/2B genes associated with type 2 diabetes in Lebanese Arab population

Nemr, Rita; Almawi, A.W.; Echtay, Akram; Sater, Mai S.; Daher, Hoda S.; Almawi, Wassim Y.

doi:10.1016/j.diabres.2011.11.002

Cited by 27 publications

(14 citation statements)

References 18 publications

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“…Our study revealed that the C allele of rs7754840 of CDKAL1 was significantly associated with T2DM in Uyghur participants ( p = 0.014, adjusted for age and BMI). The OR value of rs7754840 was 2.32, higher than that of Han Chinese (1.127) (Hu et al, 2009), Pima Indians (1.06) (Rong et al, 2009), and Lebanese Arabs (1.86) (Nemr et al, 2012). T2DM patients had a higher CC genotype and lower GG genotype of CDKAL1 when compared with the control group (Chi- ADRA2A: adrenergic a2A receptor; CDC123/CAMK1D: cell division cycle 123; CDKAL1: cyclin-dependent kinase 5 regulatory subunit associated protein 1-like 1; CDKN2A/B: cyclin-dependent kinase inhibitor-2A/B; DGKB: diacylglycerol kinase, beta 90kDa; FADS1: fatty acid desaturase 1; GCK: glucokinase; GCKR: glucokinase regulatory protein; IGF1: insulin-like growth factor 1; IGF2BP2: insulin-like growth factor 2 mRNA binding protein 2; IRS1: insulin receptor substrate 1; JAZF1: juxtaposed with another zinc finger 1; PPARG: peroxisome proliferator-activated receptor gamma; SLC30A8: solute carrier family 30 member 8; TCF7L2: transcription factor 7-like 2; TSPAN8: tetraspanin 8.…”

Section: Study Findingsmentioning

confidence: 78%

“…There are differences in the contribution of known SNPs in T2DM susceptibility genes among various ethnic populations (Klimentidis et al, 2011). SNP rs7754840 in CDKAL1, identified as T2DM susceptibility locus in subjects from Finland and Sweden by GWAS (Saxena et al, 2007), was replicated in Koreans (Lee et al, 2008), Han Chinese (Hu et al, 2009), Pima Indians (Rong et al, 2009), and Lebanese Arabs (Nemr et al, 2012), but showed inconsistency in risk allele frequencies and odds ratios (ORs) among these ethnic populations. SNP rs864745 in JAZF1 was associated with T2DM in European populations (Zeggini et al, 2008), whereas it was not found to be associated with T2DM in Chinese (Hu et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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The Uyghur Population and Genetic Susceptibility to Type 2 Diabetes: Potential Role for Variants inCDKAL1,JAZF1, andIGF1Genes

Song

Zhao

Ran

et al. 2015

OMICS: A Journal of Integrative Biology

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Substantial evidence suggests that type 2 diabetes mellitus (T2DM) is a multi-factorial disease with a strong genetic component. A list of genetic susceptibility loci in populations of European and Asian ancestry has been established in the literature. Little is known on the inter-ethnic contribution of such established functional polymorphic variants. We performed a case-control study to explore the genetic susceptibility of 16 selected T2DM-related SNPs in a cohort of 102 Uyghur objects (51 cases and 51 controls). Three of the 16 SNPs showed significant association with T2DM in the Uyghur population. There were significant differences between the T2DM and control groups in frequencies of the risk allelic distributions of rs7754840 (CDKAL1) (p=0.014), rs864745 (JAZF1) (p=0.032), and rs35767 (IGF1) (p=0.044). Carriers of rs7754840-C, rs35767-A, and rs864745-C risk alleles had a 2.32-fold [OR (95% CI): 1.19-4.54], 2.06-fold [OR (95% CI): 1.02-4.17], 0.48-fold [OR (95% CI): 0.24-0.94] increased risk for T2DM, respectively. The cumulative risk allelic scores of these 16 SNPs differed significantly between the T2DM patients and the controls [17.1±8.1 vs. 15.4±7.3; OR (95%CI): 1.27(1.07-1.50), p=0.007]. This is the first study to evaluate genomic variation at 16 SNPs in respective T2DM candidate genes for the Uyghur population compared with other ethnic groups. The SNP rs7754840 in CDKAL1, rs864745 in JAZF1, and rs35767 in IGF1 might serve as potential susceptibility loci for T2DM in Uyghurs. We suggest a broader capture and study of the world populations, including who that are hitherto understudied, are essential for a comprehensive understanding of the genetic/genomic basis of T2DM.

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Section: Study Findingsmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

The Uyghur Population and Genetic Susceptibility to Type 2 Diabetes: Potential Role for Variants inCDKAL1,JAZF1, andIGF1Genes

Song

Zhao

Ran

et al. 2015

OMICS: A Journal of Integrative Biology

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“…These variants have been found to be convincingly associated with T2DM in Caucasian populations [6][7][8][9][10][11][12][13][14]. However, recently Nemr et al [15] have found that CDKN2A/2B rs10811661 is not associated with T2DM in Lebanese.…”

Section: Introductionmentioning

confidence: 99%

Association of Common Variants of CDKN2A/2B Rs10811661 (C/T)and WFS1 Rs6446482 (C/G) to Type 2 Diabetes Mellitus in the Indian Population of Eastern Uttar Pradesh

Singh¹

2012

J Diabetes Metab

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Aim: Recent genome-wide association studies (GWAS) have identified several unsuspected genes that significantly increase the risk of type 2 diabetes mellitus (T2DM). We aimed to replicate the association of a common variant each in CDKN2A/2B (rs10811661) and WFS1 (rs6446482) in the population of Eastern Uttar Pradesh, India. These variants have been identified to be differentially associated with T2DM in different ethnic groups in previous GWAS. Results:We found SNP rs10811661 of CDKN2A/2B (OR 1.50, 95% CI 1.109-2.032, P=0.009) and SNP rs6446482 of WFS1 (OR 1.43, 95% CI 1.074-1.896, P=0.014) as significant risk factors for T2DM in Eastern Uttar Pradesh population. Normal Glucose-Tolerant (NGT) subjects carrying risk allele of rs10811661 (C/T) and rs6446482 (C/G) polymorphisms had significantly higher Fasting Plasma Glucose (FPG) and 2-hour Postprandial Plasma Glucose (2h-PPPG) levels compared to non-carriers. Conclusion:Our study replicates the association of well established common variants of CDKN2A/2B rs10811661 (C/T) and WFS1 rs6446482 (C/G) with type 2 diabetes in the population of Eastern Uttar Pradesh, India. Interestingly, our data show larger effect size for both of the SNPs than those reported in European populations.

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“…Previous replication studies examining a total of 29 SNPs in the Lebanese population have identified variants associated with T2DM in COL8A1 , KCNQ1 , ALX4 , HNF1 45 (n = 2071), CDKAL1 50 (n = 1422), and TCF7L2 4647 (n = 1610).…”

Section: Discussionmentioning

confidence: 96%

T2DM GWAS in the Lebanese population confirms the role of TCF7L2 and CDKAL1 in disease susceptibility

Ghassibe-Sabbagh

Haber

Salloum

et al. 2014

Sci Rep

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Genome-wide association studies (GWAS) of multiple populations with distinctive genetic and lifestyle backgrounds are crucial to the understanding of Type 2 Diabetes Mellitus (T2DM) pathophysiology. We report a GWAS on the genetic basis of T2DM in a 3,286 Lebanese participants. More than 5,000,000 SNPs were directly genotyped or imputed using the 1000 Genomes Project reference panels. We identify genome-wide significant variants in two loci CDKAL1 and TCF7L2, independent of sex, age and BMI, with leading variants rs7766070 (OR = 1.39, P = 4.77 × 10−9) and rs34872471 (OR = 1.35, P = 1.01 × 10−8) respectively. The current study is the first GWAS to find genomic regions implicated in T2DM in the Lebanese population. The results support a central role of CDKAL1 and TCF7L2 in T2DM susceptibility in Southwest Asian populations and provide a plausible component for understanding molecular mechanisms involved in the disease.

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Replication study of common variants in CDKAL1 and CDKN2A/2B genes associated with type 2 diabetes in Lebanese Arab population

Cited by 27 publications

References 18 publications

The Uyghur Population and Genetic Susceptibility to Type 2 Diabetes: Potential Role for Variants inCDKAL1,JAZF1, andIGF1Genes

The Uyghur Population and Genetic Susceptibility to Type 2 Diabetes: Potential Role for Variants inCDKAL1,JAZF1, andIGF1Genes

Association of Common Variants of CDKN2A/2B Rs10811661 (C/T)and WFS1 Rs6446482 (C/G) to Type 2 Diabetes Mellitus in the Indian Population of Eastern Uttar Pradesh

T2DM GWAS in the Lebanese population confirms the role of TCF7L2 and CDKAL1 in disease susceptibility

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