Common Variants of Homocysteine Metabolism Pathway Genes and Risk of Type 2 Diabetes and Related Traits in Indians

Abstract EN

Hyperhomocysteinemia, a risk factor for cardiovascular disorder, obesity, and type 2 diabetes, is prevalent among Indians who are at high risk of these metabolic disorders.

We evaluated association of common variants of genes involved in homocysteine metabolism or its levels with type 2 diabetes, obesity, and related traits in North Indians.

We genotyped 90 variants in initial phase (2.115 subjects) and replicated top signals in an independent sample set (2.085 subjects).

The variant MTHFR-rs1801133 was the top signal for association with type 2 diabetes (OR=0.78 (95% CI=0.67–0.92), P=0.003) and was also associated with 2 h postload plasma glucose (P=0.04), high-density lipoprotein cholesterol (P=0.004), and total cholesterol (P=0.01) in control subjects.

These associations were neither replicated nor significant after meta-analysis.

Studies involving a larger study population and different ethnic groups are required before ruling out the role of these important candidate genes in type 2 diabetes, obesity, and related traits.