rs7172432

A population-based association study in 5,722 non-diabetic Danish individuals from the Inter99 cohort examined the rs7172432 A allele in the VPS13C/C2CD4A/C2CD4B locus (previously associated with type 2 diabetes risk). The diabetes-associated A allele showed strong association with impaired glucose-stimulated insulin response (GSIR), with effect sizes of 3-8% reduction in GSIR per allele (β = -0.039 to -0.057, p = 2×10⁻⁷ to 9×10⁻⁹). The variant also associated with 0.60 cm higher waist circumference and 0.037 mmol/l higher fasting plasma glucose. Conditional analyses showed rs7172432 has superior effect compared to other regional SNPs (rs11071657, rs17271305), suggesting impaired beta cell function as the intermediary mechanism for type 2 diabetes risk.

This replication study in 11,530 Japanese individuals (8,552 type 2 diabetes cases, 2,978 controls) confirmed that rs10906115 in CDC123/CAMK1D and rs1359790 near SPRY2 are significantly associated with susceptibility to type 2 diabetes, with ORs of 1.15-1.17 and 1.12-1.14 respectively. Meta-analysis with the original Chinese cohort further strengthened these associations across East Asian populations, while rs1436955 in C2CD4A/C2CD4B showed nominal association and rs10751301 in ODZ4 was not significant.