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Objective: The objective was to study the association of Klotho gene G395A and C1818T single nucleotide polymorphisms with glycemia, serum, glycosylated hemoglobin (HbA1c) level and the risk of type 2 diabetes mellitus (T2DM) in the Pashtun population of Pakistan. Methods: In this study, 195 normal individuals and 217 T2DM patients were enrolled. All subjects were divided into three groups, namely overall subjects (control + T2DM patients), control individuals and T2DM patients, and their fasting glucose, HbA1c level, lipid profile and C1818T and G395A polymorphisms were determined. Results: The allele frequencies of G395A in overall subjects were 0.568 for A and 0.432 for G. Similarly, allele frequencies for G395A in overall subjects were 0.597 and 0.403 for C and T alleles, respectively. The AA genotype of G395A was observed to be a risk factor for T2DM. In normal individuals, no significant (p &gt; 0.05) association was observed between klotho C1818T and G395A polymorphisms and hyperglycemia. In overall subjects, the C1818T polymorphism was associated (p &lt; 0.05) with high fasting glucose and HbA1c levels in female subjects only. In T2DM patients, both C1818T and G395A polymorphisms were found to be significantly (p &lt; 0.05) associated with high fasting glucose and HbA1c levels both in males and females. Conclusion: The G395A polymorphism was observed to increase the risk of T2DM. Both C1818T and G395 were associated with high fasting glucose and HbA1c levels in T2DM patients.

Investigation of Klotho G395A and C1818T Polymorphisms and Their Association with Serum Glucose Level and Risk of Type 2 Diabetes Mellitus