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Meta-Analysis
. 2015 May 8;10(5):e0124662.
doi: 10.1371/journal.pone.0124662. eCollection 2015.

Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

Ekaterina Alekseevna Sokolova  1 , Irina Arkadievna Bondar  2 , Olesya Yurievna Shabelnikova  2 , Olga Vladimirovna Pyankova  1 , Maxim Leonidovich Filipenko  3
Affiliations
Meta-Analysis

Replication of KCNJ11 (p.E23K) and ABCC8 (p.S1369A) Association in Russian Diabetes Mellitus 2 Type Cohort and Meta-Analysis

Ekaterina Alekseevna Sokolova et al. PLoS One. .

Abstract

The genes ABCC8 and KCNJ11 have received intense focus in type 2 diabetes mellitus (T2DM) research over the past two decades. It has been hypothesized that the p.E23K (KCNJ11) mutation in the 11p15.1 region may play an important role in the development of T2DM. In 2009, Hamming et al. found that the p.1369A (ABCC8) variant may be a causal factor in the disease; therefore, in this study we performed a meta-analysis to evaluate the association between these single nucleotide polymorphisms (SNPs), including our original data on the Siberian population (1384 T2DM and 414 controls). We found rs5219 and rs757110 were not associated with T2DM in this population, and that there was linkage disequilibrium in Siberians (D'=0.766, r(2)= 0.5633). In addition, the haplotype rs757110[T]-rs5219[C] (p.23K/p.S1369) was associated with T2DM (OR = 1.52, 95% CI: 1.04-2.24). We included 44 original studies published by June 2014 in a meta-analysis of the p.E23K association with T2DM. The total OR was 1.14 (95% CI: 1.11-1.17) for p.E23K for a total sample size of 137,298. For p.S1369A, a meta-analysis was conducted on a total of 10 studies with a total sample size of 14,136 and pooled OR of 1.14 [95% CI (1.08-1.19); p = 2 x 10-6]. Our calculations identified causal genetic variation within the ABCC8/KCNJ11 region for T2DM with an OR of approximately 1.15 in Caucasians and Asians. Moreover, the OR value was not dependent on the frequency of p.E23K or p.S1369A in the populations.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Study selection for meta-analysis of rs5219 of KCNJ11.
Fig 2
Fig 2. Forest and funnel plots of meta-analysis of rs5219 of KCNJ11.
Fig 3
Fig 3. L’Abbe plot for KCNJ11 (p.E23K).
Fig 4
Fig 4. OR dependence on the effective sample size.
Fig 5
Fig 5. P-value dependence on the effective sample size.
Fig 6
Fig 6. Forest and funnel plots of meta-analysis of rs757110 of ABCC8.
See this image and copyright information in PMC

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