Home Life Sciences Correlation between CDKAL1 rs10946398C>A single nucleotide polymorphism and type 2 diabetes mellitus susceptibility: A meta-analysis
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Correlation between CDKAL1 rs10946398C>A single nucleotide polymorphism and type 2 diabetes mellitus susceptibility: A meta-analysis

  • Yunyi Liang , Yi Shu , Haizhao Luo , Riqiu Chen and Zhifu Zeng EMAIL logo
Published/Copyright: December 29, 2017
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Open Life Sciences
From the journal Open Life Sciences Volume 12 Issue 1

Abstract

Objective

The purpose of this meta analysis was to assess the correlation between CDKAL1 rs10946398C>A single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) susceptibility by pooling the open published studies.

Method

Electronic searching of PubMed, EMBASE, Medline, Cochrane, China Biology Medicine disc (CBM) and China National Knowledge Infrastructure (CNKI) databases were performed by two reviewers independently to collect the open published studies related to CDKAL1 rs10946398C>A single nucleotide polymorphism and T2DM susceptibility. The association between CDKAL1 rs10946398C>A single nucleotide polymorphism and T2DM susceptibility was expressed by odds ratio (OR) and the corresponding 95% confidence interval (95%CI).

Results

Thirteen studies with a total of 13,966 T2DM and 14,274 controls were finally included for analysis in this meta-analysis. Of the included 13 publications, 2 studies were carried out in Europe, 8 in Asia, 2 in Africa and 1 in Latin America. Being significant statistical heterogeneity, the data was pooled through random effect model. In a dominant genetic model, there was significant correlation between CDKAL1 rs10946398C>A SNP and T2DM risk (OR=1.22, P<0.05). In a dominant genetic model people with CC or CA genotype had increased risk of developing T2DM; Because of statistical heterogeneity for the included studies in a recessive genetic model (AA+CA vs CC), the data was calculated by random effect method. The combined data showed people with AA or CA genotype had decreased risk of developing T2DM compared to CC genotype (OR=0.83, P<0.05); For a homozygous genetic model (CC vs AA), the OR was calculated through random effect model for statistical heterogeneity among the included 13 studies. The combined OR was 1.33 which indicated people with CC genotype had increased risk of developing T2DM.

Conclusion

According to the present results, CDKAL1 rs10946398C>A single nucleotide polymorphism had correlation with the susceptibility of type 2 diabetes mellitus.

Keywords: type 2 diabetes mellitus; CDKAL1 gene; susceptibility; polymorphism; meta-analysis

1 Introduction

Type 2 diabetes mellitus (T2DM) is a metabolic disorder caused by insufficient insulin secretion or insulin resistance [1,2]. Epidemiological studies have suggested that T2DM is a multifactor genetically heterogeneous disease that involves in the effects of multiple genes and environmental factors [3,4]; thus, its pathogenesis is complex and the cause of this disease has not yet been fully elucidated. CDKAL1 is a newly identified gene that is relevant to T2DM pathogenesis [5,6]. However, research on the relationship between CDKAL1 gene rs10946398 site polymorphism and T2DM is inconclusive [7,8,9]. Wu et al. [10] evaluated the correlation between common variants of CDKAL1 gene and type 2 diabetes. The authors found in Chinese Hans, the common variants of rs10946398C>A single nucleotide polymorphism was associated with the susceptibility of type 2 diabetes mellitus. However, Cruz [9] didn’t find the correlations in all genetic models. In this study, a meta-analysis has been conducted to comprehensively and quantitatively evaluate previous study results to obtain medical evidence on the relationship between CDKAL1 gene rs10946398 polymorphism and T2DM susceptibility.

2 Methods

2.1 Publication searching

Electronic searching of PubMed, EMBASE Medline, Cochrane, China Biology Medicine disc (CBM) and China National Knowledge Infrastructure (CNKI) databases was performed by two reviewers (Yunyi Liang and Yi Shu) independently to collect the open published studies related to CDKAL1 rs10946398C>A SNP and T2DM susceptibility. The electronic searching words were described as follows: CDKAL1 gene, T2DM, susceptibility, rs10946398 and genetic polymorphism. The studies searching process was done by two reviewers (Yunyi Liang and Yi Shu) and cross checked. The references of included publications were also reviewed to find additional suitable studies.

2.2 Publication inclusion and exclusion criteria

The study inclusion criteria were: ① Open published studies about CDKAL1 rs10946398C>A SNP and T2DM susceptibility with the language restriction of English and Chinese; ② The study was restrict to case-control or cohort study; ③ The study should provide the genotype distribution; ④ The T2DM patients had confirmed diagnosis according to WHO DM diagnostic criteria; ⑤ Subjects in the control group did not have family history of DM. The publication exclusion criteria were: ① Duplicated publications; ② Case report or review study type; ③ Studies published in other language; ④ The original study did not provided genotype distribution or enough data to calculate the OR.

2.3 Data extraction

Two reviewers (Haizhao Luo and Riqiu Chen) independently reviewed the whole paper to extract the necessary information and data. The general characteristics of the included studies such as first and corresponding authors, the paper publication year, and the race of subjects were extracted and cross checked by the two reviewers. The data of genotype distribution (CC, CA and AA) for CDKAL1 rs10946398 from each included studies were also extracted. The data was cross examined by the two reviewers to make consensus. A third reviewer (Fuzhi Zeng) was consulted if disagreement was encountered.

2.4 Statistical analysis

Stata 11.0 (for meta-analysis) was used to deal with the data analysis. Firstly, the data extracted from each included publication was tested for statistical heterogeneity through chi-square test [11] and the inconsistency was calculated by I2 [12].If significant statistical heterogeneity existed among the included studies, the data was pooled by random effect method otherwise the data was calculated by fixed effect methods. The odds ratio (OR) was used to demonstrate the correlation between DKAL1 rs10946398C>A single nucleotide polymorphism and T2DM susceptibility. The publication bias was evaluated by Begg’s funnel plot and Egger’s line regression test. Two tail p≤0.05 was considered statistical significance.

3 Results

3.1 General characteristics of the included thirteen studies

After searching the electronic databases, 364 publications were initially identified. After reading the title, abstract and full text paper, 351 studies were did not meet the inclusion criteria and were excluded. 13 studies [7,8,9,10, 13,14,15,16,17,18,19,20,21] with a total of 13966 T2DM and 14274 controls were finally included for analysis in this meta-analysis, Figure 1. Of the included 13 publications, 2 studies were carried out in Europe, 8 in Asia, 2 in Africa and 1 in Latin America. The detailed information for the included studies were showed in Table 1.

Table 1

General information for the included studies

AuthorsYearRegionRaceCaseControl
CCCAAACCCAAA
Grarup [13]2007EuropeCaucasus184424244159422281
Scott [7]2007EuropeCaucasus171549440150539486
Lewis [14]2008AfricaAfrican353442138357513185
Wu [10]2008AsiaEast Asian106212106319922666
Hu [8]2009AsiaEast Asian360912578306866613
Cruz [9]2010Latin AmericaAmerica5222524251224244
Han [15]2010AsiaEast Asian227498273177484330
Lin [16]2010AsiaEast Asian310757463195666567
Wen [17]2010AsiaEast Asian226574365175542420
Cooke [18]2012AfricaAfrican9681269416453683258
Chen [19]2013AsiaEast Asian97221125296559264
Al-Sinani [20]2015AsiaEuropa40146013114012628
Sun [21]2015AsiaEast Asian10823110899294215

Figure 1 Publication inclusion flow-chart of this meta-analysis
Figure 1

Publication inclusion flow-chart of this meta-analysis

3.2 Genotype distribution

The median CC, CA and AA genotype distribution frequency for T2DM group were 0.22, 0.49 and 0.28. And for control group, the median distribution frequency CC, CA and AA genotype were 0.18, 0.48 and 0.34 respectively. There was no statistical difference for the CC, CA and AA genotype distribution between the two groups (P>0.05), Figure 2.

Figure 2 Scatter plot of genotype distribution in DM and control group (a: CC genotype distribution; b: CA genotype distribution; c: AA genotype distribution).
Figure 2

Scatter plot of genotype distribution in DM and control group (a: CC genotype distribution; b: CA genotype distribution; c: AA genotype distribution).

3.3 Statistical heterogeneity evaluation

The statistical heterogeneity for the included studies were evaluate by I2 test. In the dominant genetic model (CC+CA vs AA), the I2=71.4% indicating significant statistical heterogeneity was existed. For the recessive genetic model (AA +CC vs CC), the statistical heterogeneity was significant with I2=73.0%. Significant heterogeneity also found in homozygous genetic model (CC vs AA) with the I2=79.7%.

3.4 Dominant genetic model (CC+CA vs AA)

For significant heterogeneity, the data was pooled through random effect model. In dominant genetic model, there was significant correlation between CDKAL1 rs10946398C>A single nucleotide polymorphism (OR=1.22, P<0.05). In dominant genetic model people with CC or CA genotype had increased risk of developing DM (Figure 3).

Figure 3 Forest plot of OR with a random-effects model for evaluation of CDKAL1 rs10946398C>A single nucleotide polymorphism and type 2 diabetes mellitus susceptibility in dominant genetic model (CC+CA vs AA)
Figure 3

Forest plot of OR with a random-effects model for evaluation of CDKAL1 rs10946398C>A single nucleotide polymorphism and type 2 diabetes mellitus susceptibility in dominant genetic model (CC+CA vs AA)

3.5 Recessive genetic model (AA+CA vs CC)

Because of statistical heterogeneity across the studies in recessive genetic model (AA+CA vs CC), the data was calculated by random effect model. The combined data showed people with AA or CA genotype had decreased risk of developing T2DM compared to CC genotype (OR=0.83, P<0.05), Figure 4.

Figure 4 Forest plot of OR with a random-effects model for evaluation of CDKAL1 rs10946398C>A single nucleotide polymorphism and type 2 diabetes mellitus susceptibility in recessive genetic model (AA+CA vs CC)
Figure 4

Forest plot of OR with a random-effects model for evaluation of CDKAL1 rs10946398C>A single nucleotide polymorphism and type 2 diabetes mellitus susceptibility in recessive genetic model (AA+CA vs CC)

3.6 Homozygous genetic model (CC vs AA)

For homozygous genetic model (CC vs AA), the OR was calculated through random effect model because of statistical heterogeneity among the included 13 studies. The combined OR was 1.33 which indicated people with CC genotype had increased of developing T2DM, Figure 5.

Figure 5 Forest plot of OR with a random-effects model for evaluation of CDKAL1 rs10946398 C>A single nucleotide polymorphism and type 2 diab
Figure 5

Forest plot of OR with a random-effects model for evaluation of CDKAL1 rs10946398 C>A single nucleotide polymorphism and type 2 diab

3.7 Publications bias

The publication bias of this meta-analysis was evaluated by both Begg’s funnel plot and Egger’s line regression test. For dominant genetic model (CC+CA vs AA). The Begg’s funnel plot was upper and lower symmetry (Figure 6). Egger’s line regression test indicated no publications bias (P=0.34). In recessive (AA+CA vs CC), (Figure 7) and homozygous (CC vs AA), (Figure 8) genetic model the Begg’s funnel plot was seemingly asymmetry. However, the Egger’s line regression test demonstrated no publication bias (P=0.72, P=0.36).

Figure 6 The Begg’s funnel plot for evaluation publication bias in dominant genetic model (CC+CA vs AA)
Figure 6

The Begg’s funnel plot for evaluation publication bias in dominant genetic model (CC+CA vs AA)

Figure 7 The Begg’s funnel plot for evaluation publication bias in recessive genetic model (AA+CA vs CC)
Figure 7

The Begg’s funnel plot for evaluation publication bias in recessive genetic model (AA+CA vs CC)

Figure 8 The Begg’s funnel plot for evaluation publication bias in Homozygous genetic model (CC vs AA)
Figure 8

The Begg’s funnel plot for evaluation publication bias in Homozygous genetic model (CC vs AA)

4 Discussion

Insulin resistance is the major pathogenesis of T2DM in humans [22,23]. As a multifactor genetically heterogeneous disease, the pathogenesis and prognosis of T2DM are caused by a combination of inherited and acquired risk factors. Literature on the screening of candidate genes related to T2DM have shown that the variation in some genes related to insulin secretion and blood sugar metabolism is certainly correlated with the occurrence and development of T2DM [24].

A number of case-control studies have revealed that single-nucleotide polymorphisms in multiple loci of CDKAL1 gene are related to T2DM pathogenesis[9, 13, 16]. The risk that the population with a specific genotype suffers from T2DM is significantly increased. However, some studies have reported that the single-nucleotide polymorphism of CDKAL1 genes is not associated with susceptibility to T2DM[9]. CDKAL1 gene is located on the short arm of chromosome 6, with a full length of 697948bp, encoding a 65ku protein. The changes in CDKAL1 gene expression can lead to the decrease in ATP and cause a KATP channel response induced by glucose to weaken. The activity of Ca2+ channel is then impaired, and first-phase insulin secretion is decreased. Studies have also shown that CDKAL1 can inhibit the activity of pancreatic β cells CDK5 under high glucose toxicity and prevent the decline in insulin gene caused by sugar toxicity[25]. Thus, insulin secretion is decreased, and the insulin secretion of people with rs10946398 dangerous allele after glucose load is also decreased. CDKAL1 gene influencing the secretion function of pancreatic β cells is related to insufficient insulin secretion but not to insulin resistance[26].

In this study, meta-analysis is conducted for 13 studies of CDKAL1 rs10946398C>A SNP from different regions. Results showed that population carrying C allele has a significantly increasing risk of suffering from T2DM. Thereafter, CDKAL1 rs10946398C>A single nucleotide polymorphism had correlation with the susceptibility of type 2 diabetes mellitus.

However, meta-analysis also has limitations. First, statistical heterogeneity exists among the included various studies. The presence of statistical heterogeneity reduces the stability of conclusions. Second, meta-analysis is only conducted for one of CDKAL1 gene SNP loci, but the interaction among polymorphic loci has not been explored yet.

No.15 Dazhong Road, Liandu District Lishui City Zhejiang Province, 323000 PR China

  1. Ethical approval: The conducted research is not related to either human or animals use.

  2. Conflict of interest: Authors state no conflict of interest

Reference

[1] Szendroedi J, Phielix E, Roden M. The role of mitochondria in insulin resistance and type 2 diabetes mellitus[J]. Nat Rev Endocrinol, 2011,8(2):92-103.10.1038/nrendo.2011.138Search in Google Scholar

[2] Małecki MT. [Obesity--insulin resistance--type 2 diabetes mellitus][J]. Kardiol Pol, 2006,64(10 Suppl 6):S561-6.Search in Google Scholar

[3] Imperato PJ, Imperato GH. The role of genealogy and clinical family histories in documenting possible inheritance patterns for diabetes mellitus in the pre-insulin era: part 2. Genealogic evidence for type 2 diabetes mellitus in Josephine Imperato’s paternal and maternal lineages[J]. J Community Health, 2009, 34(6):553-85.10.1007/s10900-009-9183-3Search in Google Scholar

[4] Sheu WH, Song YM, Lee WJ, et al. Family aggregation and maternal inheritance of Chinese type 2 diabetes mellitus in Taiwan[J]. Zhonghua Yi Xue Za Zhi (Taipei), 1999,62(3):146-51.Search in Google Scholar

[5] Nikitin AG, Potapov VY, Brovkina OI, et al. Association of polymorphic markers of genes FTO, KCNJ11, CDKAL1, SLC30A8, and CDKN2B with type 2 diabetes mellitus in the Russian population[J]. PeerJ, 2017,5:e3414.10.7717/peerj.3414Search in Google Scholar

[6] Kommoju UJ, Samy SK, Maruda J, et al. Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India[J]. Indian J Med Res, 2016,143(4):455-63.10.4103/0971-5916.184303Search in Google Scholar

[7] Scott LJ, Mohlke KL, Bonnycastle LL, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants[J]. Science, 2007,316(5829):1341-5.10.1126/science.1142382Search in Google Scholar

[8] Hu C, Zhang R, Wang C, et al. PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population[J]. PLoS One, 2009,4(10):e7643.10.1371/journal.pone.0007643Search in Google Scholar

[9] Cruz M, Valladares-Salgado A, Garcia-Mena J, et al. Candidate gene association study conditioning on individual ancestry in patients with type 2 diabetes and metabolic syndrome from Mexico City[J]. Diabetes Metab Res Rev, 2010,26(4):261-70.10.1002/dmrr.1082Search in Google Scholar

[10] Wu Y, Li H, Loos RJ, et al. Common variants in CDKAL1, CDKN2A/B, IGF2BP2, SLC30A8, and HHEX/IDE genes are associated with type 2 diabetes and impaired fasting glucose in a Chinese Han population[J]. Diabetes, 2008,57(10):2834-42.10.2337/db08-0047Search in Google Scholar

[11] DerSimonian R, Laird N. Meta-analysis in clinical trials[J]. Control Clin Trials, 1986,7(3):177-88.10.1016/0197-2456(86)90046-2Search in Google Scholar

[12] Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses[J]. BMJ (Clinical research ed.), 2003,327(7414):557-60.10.1136/bmj.327.7414.557Search in Google Scholar PubMed PubMed Central

[13] Grarup N, Rose CS, Andersson EA, et al. Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies[J]. Diabetes, 2007,56(12):3105-11.10.2337/db07-0856Search in Google Scholar PubMed

[14] Lewis JP, Palmer ND, Hicks PJ, et al. Association analysis in african americans of European-derived type 2 diabetes single nucleotide polymorphisms from whole-genome association studies[J]. Diabetes, 2008,57(8):2220-5.10.2337/db07-1319Search in Google Scholar PubMed PubMed Central

[15] Han X, Luo Y, Ren Q, et al. Implication of genetic variants near SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, FTO, TCF2, KCNQ1, and WFS1 in type 2 diabetes in a Chinese population[J]. BMC Med Genet, 2010,11:81.10.1186/1471-2350-11-81Search in Google Scholar PubMed PubMed Central

[16] Lin Y, Li P, Cai L, et al. Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population[J]. BMC Med Genet, 2010,11:97.10.1186/1471-2350-11-97Search in Google Scholar PubMed PubMed Central

[17] Wen J, Rönn T, Olsson A, et al. Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort[J]. PLoS One, 2010,5(2):e9153.10.1371/journal.pone.0009153Search in Google Scholar PubMed PubMed Central

[18] Cooke JN, Ng MC, Palmer ND, et al. Genetic risk assessment of type 2 diabetes-associated polymorphisms in African Americans[J]. Diabetes Care, 2012,35(2):287-92.10.2337/dc11-0957Search in Google Scholar PubMed PubMed Central

[19] Chen G, Xu Y, Lin Y, et al. Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population[J]. J Diabetes, 2013,5(2):136-45.10.1111/1753-0407.12025Search in Google Scholar PubMed

[20] Al-Sinani S, Woodhouse N, Al-Mamari A, et al. Association of gene variants with susceptibility to type 2 diabetes among Omanis[J]. World J Diabetes, 2015,6(2):358-66.10.4239/wjd.v6.i2.358Search in Google Scholar PubMed PubMed Central

[21] Sun XF, Xiao XH, Zhang ZX, et al. Positive Association Between Type 2 Diabetes Risk Alleles Near CDKAL1 and Reduced Birthweight in Chinese Han Individuals[J]. Chin Med J (Engl), 2015,128(14):1873-8.10.4103/0366-6999.160489Search in Google Scholar PubMed PubMed Central

[22] Czech MP. Insulin action and resistance in obesity and type 2 diabetes[J]. Nat Med, 2017,23(7):804-814.10.1038/nm.4350Search in Google Scholar PubMed PubMed Central

[23] Gougeon R. Insulin resistance of protein metabolism in type 2 diabetes and impact on dietary needs: a review[J]. Can J Diabetes, 2013,37(2):115-20.10.1016/j.jcjd.2013.01.007Search in Google Scholar PubMed

[24] Barroso I, Luan J, Middelberg RP, et al. Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action[J]. PLoS Biol, 2003,1(1):E20.10.1371/journal.pbio.0000020Search in Google Scholar PubMed PubMed Central

[25] Brambillasca S, Altkrueger A, Colombo SF, et al. CDK5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is a tail-anchored protein in the endoplasmic reticulum (ER) of insulinoma cells[J]. J Biol Chem, 2012,287(50):41808-19.10.1074/jbc.M112.376558Search in Google Scholar PubMed PubMed Central

[26] Lyssenko V, Jonsson A, Almgren P, et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes[J]. N Engl J Med, 2008,359(21):2220-32.10.1056/NEJMoa0801869Search in Google Scholar PubMed

Received: 2017-9-19
Accepted: 2017-10-17
Published Online: 2017-12-29

© 2017 Yunyi Liang et al.

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

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https://doi.org/10.1515/biol-2017-0059
Keywords for this article
type 2 diabetes mellitus; CDKAL1 gene; susceptibility; polymorphism; meta-analysis
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