Polymorphisms in Genes of Lipid Metabolism Are Associated with Type 2 Diabetes Mellitus and Periodontitis, as Comorbidities, and with the Subjects’ Periodontal, Glycemic, and Lipid Profiles

Abstract

Background. Type 2 diabetes mellitus (T2DM) and periodontitis (P) commonly occur as comorbidities, but the commonalities in the genetic makeup of affected individuals is largely unknown. Since dyslipidemia is a frequent condition in these individuals, we investigate the association of genomic variations in genes involved in lipid metabolism with periodontal, glycemic, lipid profiles, and the association with periodontitis and T2DM (as comorbidities). Methods. Based on clinical periodontal examination and biochemical evaluation, 893 subjects were divided into T2DM+P (T2DM subjects also affected by periodontitis, n = 205 ), periodontitis ( n = 345 ), and healthy ( n = 343 ). Fourteen single-nucleotide polymorphisms (SNPs) were investigated: LDLR gene (rs5925 and rs688), APOB (rs676210, rs1042031, and rs693), ABCC8 (rs6544718 and 6544713), LPL (rs28524, rs3735964, and rs1370225), HNF1A (rs2650000), APOE (rs429358 and rs7412), and HNF4A (rs1800961). Multiple linear and logistic regressions (adjusted for covariates) were made for all populations and stratified by sex and smoking habits. Results. Individuals carrying APOB-rs1042031-CT (mainly women and never smokers) had a lower risk of developing periodontitis and T2DM (T2DM+P); altogether, this genotype was related with healthier glycemic, lipid, and periodontal parameters. Significant disease-phenotype associations with gene-sex interaction were also found for carriers of APOB-rs1676210-AG, HNF4A-rs1800961-CT, ABCC8-rs6544718-CT, LPL-rs13702-CC, and LPL-rs285-CT. Conclusions. Polymorphisms in lipid metabolism genes are associated with susceptibility to T2DM-periodontitis comorbidities, demonstrating gene-sex interaction. The APOB-rs1042031 was the most relevant gene marker related to glucose and lipid metabolism profiles, as well as with obesity and periodontitis.

The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: A quasi-experimental study

“…However, we were able to observe that more female patients were present. This consistent with previous research which reports that women are more susceptible to both conditions and exhibit a higher degree of severity 50 . As a result of the increase in levels of steroidal hormones, bone metabolism, and in ammation.…”

Association between HNF4A rs1800961 polymorphisms and gallstones in a Taiwanese population

“…Another explanation for the higher gallstone prevalence in obese patients with the HNF4A variant is that HNF4A polymorphism has been reported to be associated with insulin resistance. [30][31][32] Increasing evidence suggests that insulin resistance results in gallbladder dysmotility and altered bile secretion. [33][34][35] Thus, the lithogenic effect of the HNF4A rs1800961 variant may be related to insulin resistance, which is highly prevalent in obese patients.…”

“…Another explanation for the higher gallstone prevalence in obese patients with the HNF4A variant is that HNF4A polymorphism has been reported to be associated with insulin resistance 30–32 . Increasing evidence suggests that insulin resistance results in gallbladder dysmotility and altered bile secretion 33–35 .…”

Visualized analysis of hotspots and frontiers in diabetes-associated periodontal disease research: a bibliometric study

“…The literature also described new techniques used to further study gene–environment interaction, which can help predict individual morbidity of periodontitis and diabetes. There were some interesting findings of single-nucleotide polymorphisms (SNPs) demonstrating that polymorphisms in lipid metabolism genes may be associated with susceptibility to diabetes-associated periodontitis ( 63 ). The TNF-α rs1800629 polymorphism might affect the risk of diabetes-associated periodontitis, particularly in individuals of Asian descent ( 28 ).…”