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

Singh, Sarva Jit

doi:10.4172/2155-6156.1000227

Cited by 3 publications

(4 citation statements)

References 26 publications

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“…Although another study constituting samples from northern and western India 4 showed strong association of CDKAL1 with T2DM, the single SNP studied was different from those of the present study. The rs10811661 of CDKN2A/B also showed strong association with T2DM in our population as was the case with north and western Indian studies 4 5 . However, the variant near HHEX gene (rs1111875) was not significantly associated with T2DM in our study similar to other Indian populations studied 2 3 .…”

Section: Discussionsupporting

confidence: 83%

“…Comparison with earlier studies among Indian populations : Despite unique Indian population structure with large number of endogamous groups and enormous ethnic, linguistic and geographic heterogeneity, very few studies have hitherto focused on replication of earlier findings of genetic association of T2DM 2 3 4 5 . The risk allele frequencies of all the SNPs considered in our study were compared with other Indian studies ( Table IV ).…”

Section: Resultsmentioning

confidence: 86%

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Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India

Kommoju¹,

Samy²,

Maruda³

et al. 2016

Indian J Med Res

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Background & objectives:The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A/B and HHEX) with T2DM in the population of Hyderabad, south India.Methods:A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A/B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform.Results:The risk allele frequencies of the CDKAL1 and CDKN2A/B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. The HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology.Interpretation & conclusions:A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A/B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population.

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Section: Discussionsupporting

confidence: 83%

Section: Resultsmentioning

confidence: 86%

Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India

Kommoju¹,

Samy²,

Maruda³

et al. 2016

Indian J Med Res

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“…Chauhan et al [89] have replicated association of eight well established genetic variants with T2D in north-western Indian populations showing higher effect size compared to the Europeans. We have also shown higher effect size compared to European populations of two of the well established genetic variants in eastern Uttar Pradesh population of India [91].…”

Section: Current Status In Indian Populationmentioning

confidence: 81%

Genetics of Type 2 Diabetes: Advances and Future Prospect

2015

J Diabetes Metab

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Type 2 diabetes (T2D) is a complex metabolic disorder with an increasing incidence worldwide. The disease is characterized by a combination of impairment in insulin secretion from pancreatic beta cells and insulin resistance of peripheral tissues, especially muscle and liver, resulting from interaction between multiple environmental and genetic factors. Life-style changes and obesity are the major causes for the current epidemic of T2D. The rapidly increasing prevalence of Type 2 diabetes makes it a major healthcare problem worldwide. In the developing nations this poses a serious health care burden. In recent years there has been a swing in the onset to younger age group. To date, Genome-Wide Association Scan (GWAS) studies have identified more than 65 common genetic variants associated with T2D or glucose/insulin levels. The recently discovered genes by GWAS suggest a shift from genes involved in insulin action to those involved in insulin secretion, indicating pivotal role of beta-cell dysfunction in the pathogenesis of T2D. However, in most cases the causal variants are not known. Also, the molecular mechanism of the patho-physiology of the disease is still obscure. Functional studies will be required to identify the mechanisms by which the associated signals impair islet function and increase risk of T2D. Understanding the pathophysiology of T2D will provide new and useful information(s) for prevention of the disease and development of new drugs for the treatment of T2D. Pharmacogenetics is another promising clinical application of the genetic findings for T2D. Also, efforts are being made to understand the genetic basis of differences in disease susceptibility by studying the genetic variations among different populations, an area that is important for the future of medicine.

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“…Genotyping of the FTO polymorphism was carried out using allele-specific PCR. Primers, enzymes, and reaction conditions for the rest of the SNPs were as previously reported [15][16][17][18][19][20][21][22][23]32]. Sequences of the PCR primers employed in this work are presented in Table 3.…”

Section: Issn: 2475-5591mentioning

confidence: 99%

Genetic Polymorphism and Risk of having Type 2 Diabetes in a Palestinian Population: A Study of 16 Gene Polymorphisms

2018

Adv Diabetes Endocrinol

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Background: Type 2 Diabetes (T2D) is a multifactorial disease that encompasses environmental risk factors and the contribution of multiple genomic variants. Studies on the genetic components of T2D revealed many T2D-associated genetic polymorphisms in various populations. Lack of studies on the relation between gene polymorphism and T2D in Palestinians prompted us to examine the association between 16 known single nucleotide polymorphisms (SNPs) and T2D in this unexplored population. Method: In this case-control study, 100 T2D male patients and 100 control men were examined. The two groups were genotyped for the 16 genes polymorphisms using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) technique. Body Mass Index (BMI), and essential clinical parameters were measured for all the study participants. The relation between the 16 SNPs and T2D were statistically analyzed using appropriate tests. Results: Significant association was evident between IGF2BP and T2D, followed by CDKN2A/B (rs10811661) (OR=2.35, P-value=0.003), COL8A1 (rs792837) (OR=2.03, P-value=0.015), KCNQ1 (rs2237892) (OR=0.184, P-value=0.017), and KCNJ11 (rs5219; E23K) (OR=1.81, P-value=0.04), based on Armitage trend test. Among the 16 tested polymorphisms, a highly statistically significant association was evident between IGF2BP2 (rs4402960) and T2D [Odds ratio (OR)=3.28, P-value=7.46x10-8]. Conclusion: IGF2BP, CDKN2A/B, COL8A1, KCNQ1, and KCNJ11 gene variants are associated with T2D in the investigated population. This preliminary study sheds some light on the genetic components of T2D in Palestine.

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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

Cited by 3 publications

References 26 publications

Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India

Association of CDKAL1, CDKN2A/B & HHEX gene polymorphisms with type 2 diabetes mellitus in the population of Hyderabad, India

Genetics of Type 2 Diabetes: Advances and Future Prospect

Genetic Polymorphism and Risk of having Type 2 Diabetes in a Palestinian Population: A Study of 16 Gene Polymorphisms

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