The Relationship Between LRP-5 and LRP-6 Gene Mutations and Postmenopausal Type 2 Diabetes and Obesity

Single nucleotide polymorphisms (SNPs) in the low-density lipoprotein receptor-related protein 5 (LRP5) and the low-density lipoprotein receptor-related protein 5 (LRP6) genes have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity (OB). This study aimed to evaluate the polymorphisms in LRP5 and LRP6 genes in postmenopausal patients with T2DM and OB.

Participants were categorized into the Non-T2DM group (n = 53) and the T2DM group (n = 89) based on glycemic levels. Baseline data and biochemical indices were collected, Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry, and SNPs at the LRP5 and LRP6 loci were assessed by time-of-flight mass spectrometry.

1. There was a statistical difference in the distribution of genotypes (CC/CT) at locus rs4988331 (χ2 = 67.940, P = .000) and in the distribution of alleles (C/T) between the T2DM and non-T2DM groups (χ2 = 50.506, P = .000). Additionally, there were significant differences in the allele (G/A) at locus rs11054704, and both allele (G/T) and genotype (GG/GT) distributions at locus rs1181334 between the OB group and the normal weight group (P < .05). 2. OB was identified as a risk factor for T2DM in individuals with the wild-type at locus rs1181334, and the interaction between wild-type and mutant was significant (P < .05). 3. Multifactorial logistic regression analysis revealed that BMD (OR 3.755; 95% CI, 1.215-11.608) and triglyceride-glucose (TyG) index (OR 2.855; 95% CI, 1.361-5.986) were risk factors for T2DM in postmenopausal women, whereas alkaline phosphatase (ALP; OR 0.970; 95% CI, 0.945-0.995) and rs4988331 mutation (OR 0.018; 95% CI, 0.006-0.060) were protective factors.

Mutations at the LRP5-rs4988331 locus, as well as the LRP6-rs11054704 and rs1181334 loci, may be associated with the development of T2DM and OB in postmenopausal women.