Association of Haptoglobin Polymorphism With Microvascular Complications in Type 2 Diabetes Mellitus: A Case-Control Study From a Tertiary Care Center in South India.

Background Type 2 diabetes mellitus (T2DM) is a major public health problem in India, with microvascular complications contributing substantially to morbidity. Haptoglobin (Hp) polymorphisms, particularly the Hp2-2 genotype, have been associated with increased oxidative stress and vascular dysfunction. This case-control study aimed to evaluate the association between Hp polymorphisms and microvascular complications in T2DM patients attending a tertiary care center in South India. Methods A hospital-based case-control study was conducted between July 2023 and December 2024. Eighty-four T2DM patients were enrolled, including 42 cases with documented microvascular complications (nephropathy, retinopathy, and/or neuropathy) and 42 controls without complications. Haptoglobin genotypes (Hp1-1, Hp2-1, Hp2-2) were determined using polymerase chain reaction with sequence-specific primers. Clinical and biochemical parameters, including glycated hemoglobin (HbA1c), lipid profile, and renal function markers, were recorded. Group comparisons were performed using appropriate parametric and non-parametric tests. A p-value <0.05 was considered statistically significant. The study was approved by the Institutional Ethics Committee, and informed consent was obtained from all participants. Results The Hp2-2 genotype was significantly more prevalent among cases compared with controls (62.5-83.3% across complication subgroups vs. 26.2% in controls). Significant associations were observed between Hp2-2 and diabetic nephropathy (p=0.001), neuropathy (p=0.003), and retinopathy (p=0.002). Patients with complications demonstrated higher mean HbA1c levels (8.51 ± 2.20% vs. 7.92 ± 1.29%, p=0.038) and a greater prevalence of microalbuminuria (78.6% vs. 11.9%, p<0.001). Conclusion The Hp2-2 genotype is strongly associated with the presence of microvascular complications in patients with T2DM. These findings suggest that Hp genotyping may have potential utility in identifying individuals at increased risk for diabetic microvascular disease.