Journal of Scientific and Technical Research (Sharda University, Noida)

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Genetic Association of a Polymorphic Variant (rs7903146) in TCF7L2 Gene by Allele-Specific Genotyping to Predict the Susceptibility of T2DM


Affiliations
1 Department of Zoology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
2 School of Sciences (Zoology), Maulana Azad Urdu University, Hyderabad, India
3 Department of Statistics and Operations Research, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
4 Rajiv Gandhi Centre for Diabetes and Endocrinology, J. N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
5 Department of Human Genetics, Guru Nanak Dev University (GNDU), Amritsar, Punjab, India
6 School of Biosciences and Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, Jammu & Kashmir, India
     

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In type 2 diabetes mellitus (T2DM), transcription factor 7- like 2 (TCF7L2) gene has been linked its susceptibility in multiple ethnicities. This case-control study investigates the possible role of TCF7L2 variant; rs7903146 (C/T) along with anthropometric data and clinical profiles in the North Indian population. TCF7L2 polymorphism was genotyped by allele-specific PCR assay. Odds ratio (OR) and 95% Confidence Intervals were used to assess the strength of genetic association. A total of 500 human subjects consisting of 250 T2DM patients together with 250 normoglycemic controls from the region of North India. Out of total T2DM subjects, 64.4% had a family history and 74% were reported to be hypertensive. Most of the anthropometric markers showed a statistically significant (p<0.0001) association with T2DM when compared to normoglycemic controls, specifically in fasting glucose, postprandial glucose, and HbA1c. Further analysis indicates that recessive genetic model of association established that the unadjusted odds ratio of risk homozygous (TT) subjects was 2.6 fold higher (OR=2.63; 95% CI=1.27-5.43) compared to wild homozygous (CC) subjects. Simultaneously, when adjusted with age, sex, and BMI, this risk was increased up to 3.4 fold (OR=3.46; 95% CI=1.63-7.34). Risk alleles (TT subjects) were also found to be statistically significant in BMI and blood sugar parameters. This SNP was also showed significant statistical association with T2DM under dominant and co-dominant models of logistic regression even after adjusting the covariates. This study exposed the positive genetic association of the risk variant rs7903146 (T) SNP of TCF7L2 in T2DM subjects of the North India.

Keywords

rs7903146, Single Nucleotide Polymorphism, TCF7L2, Type 2 Diabetes Mellitus (T2DM).
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  • Genetic Association of a Polymorphic Variant (rs7903146) in TCF7L2 Gene by Allele-Specific Genotyping to Predict the Susceptibility of T2DM

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Authors

Monika Sharma
Department of Zoology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
Arif Ahmad
School of Sciences (Zoology), Maulana Azad Urdu University, Hyderabad, India
Arti Sharma
Department of Statistics and Operations Research, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
Jamal Ahmad
Rajiv Gandhi Centre for Diabetes and Endocrinology, J. N. Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
Badaruddoza
Department of Human Genetics, Guru Nanak Dev University (GNDU), Amritsar, Punjab, India
Riaz Ahmad
Department of Zoology, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
Iqbal Parwez
School of Biosciences and Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, Jammu & Kashmir, India

Abstract


In type 2 diabetes mellitus (T2DM), transcription factor 7- like 2 (TCF7L2) gene has been linked its susceptibility in multiple ethnicities. This case-control study investigates the possible role of TCF7L2 variant; rs7903146 (C/T) along with anthropometric data and clinical profiles in the North Indian population. TCF7L2 polymorphism was genotyped by allele-specific PCR assay. Odds ratio (OR) and 95% Confidence Intervals were used to assess the strength of genetic association. A total of 500 human subjects consisting of 250 T2DM patients together with 250 normoglycemic controls from the region of North India. Out of total T2DM subjects, 64.4% had a family history and 74% were reported to be hypertensive. Most of the anthropometric markers showed a statistically significant (p<0.0001) association with T2DM when compared to normoglycemic controls, specifically in fasting glucose, postprandial glucose, and HbA1c. Further analysis indicates that recessive genetic model of association established that the unadjusted odds ratio of risk homozygous (TT) subjects was 2.6 fold higher (OR=2.63; 95% CI=1.27-5.43) compared to wild homozygous (CC) subjects. Simultaneously, when adjusted with age, sex, and BMI, this risk was increased up to 3.4 fold (OR=3.46; 95% CI=1.63-7.34). Risk alleles (TT subjects) were also found to be statistically significant in BMI and blood sugar parameters. This SNP was also showed significant statistical association with T2DM under dominant and co-dominant models of logistic regression even after adjusting the covariates. This study exposed the positive genetic association of the risk variant rs7903146 (T) SNP of TCF7L2 in T2DM subjects of the North India.

Keywords


rs7903146, Single Nucleotide Polymorphism, TCF7L2, Type 2 Diabetes Mellitus (T2DM).

References