Association of CYP19A1 and CYP1A2 genetic polymorphisms with type 2 diabetes mellitus risk in the Chinese Han population

Abstract

Background: Type 2 diabetes mellitus (T2DM), one of the global health issues, is a group of metabolic diseases and is affected by several genetic loci in the clinical phenotype. This study intended to ascertain associations between CYP19A1 and CYP1A2 gene polymorphisms with the T2DM risk in Chinese Han. Methods: Seven single nucleotide polymorphisms (SNPs) in total including five of CYP19A1 (rs4646, rs6493487, rs1062033, rs17601876 and rs3751599) and two of CYP1A2 (rs762551 and rs2470890) from 512 T2DM patients and 515 non-diabetic controls were genotyped in the platform of Agena MassARRAY. SPSS 18.0 was utilized for analyzing genotyping results. Logistic regression models were conducted for the risk assessment by the odds ratios (ORs) and 95% confidence intervals (CIs). Results: The results suggested a significant association between genotype GC of rs1062033 with a decreased T2DM risk (OR = 0.73, 95% CI = 0.55-0.96, P = 0.025) under the co-dominant (heterozygous) model. The results of stratification analysis with age and gender adjustment revealed that the effects of all selected SNPs in CYP19A1 and CYP1A2 on the T2DM susceptibility were dependent on age, body mass index (BMI) and disease progression (P < 0.05). The haplotype analysis was further conducted and the results indicated that C rs1062033 G rs17601876 A rs3751599 in CYP19A1 played a protective role (OR = 0.48, 95% CI = 0.25-0.91, P = 0.026) in T2DM patients with diabetic retinopathy. Conclusion: This population-based case-control study suggested that CYP19A1 and CYP1A2 variations might affect the susceptibility of T2DM. The findings provide a theoretical basis for searching the clinical therapeutic markers and attractive drug targets of T2DM.

Vitamin D: Can Gender Medicine Have a Role?

“…As we have said, vitamin D performs multiple functions in our body and is involved in many diseases. Most of the actions performed by vitamin D are related to its intake and the affinity of its precursors with the vitamin D nuclear receptor (VDR) [ 27 , 28 ]. The VDR is expressed in organs, such as the gut, skeleton, and parathyroid gland in the ovaries and testicles; above all, the function of vitamin D at the level of both sexes is poorly understood [ 27 , 28 ].…”

“…Most of the actions performed by vitamin D are related to its intake and the affinity of its precursors with the vitamin D nuclear receptor (VDR) [ 27 , 28 ]. The VDR is expressed in organs, such as the gut, skeleton, and parathyroid gland in the ovaries and testicles; above all, the function of vitamin D at the level of both sexes is poorly understood [ 27 , 28 ]. It has been observed that vitamin D and estrogen have a double relationship in the sense that low levels of estrogen are associated with falls of osteopenia or rickets, while it has been seen that VDR at the level gonadal plays a role in the production of estrogen [ 27 , 28 ].…”

“…The VDR is expressed in organs, such as the gut, skeleton, and parathyroid gland in the ovaries and testicles; above all, the function of vitamin D at the level of both sexes is poorly understood [ 27 , 28 ]. It has been observed that vitamin D and estrogen have a double relationship in the sense that low levels of estrogen are associated with falls of osteopenia or rickets, while it has been seen that VDR at the level gonadal plays a role in the production of estrogen [ 27 , 28 ]. It has been showed that vitamin D regulates the biosynthesis of estrogens by means of calcitropic activity and by maintaining the homeostasis of intracellular and extracellular calcium in balance and by acting directly in the regulation of the expression of the aromatase gene [ 28 ].…”

“…It has been observed that vitamin D and estrogen have a double relationship in the sense that low levels of estrogen are associated with falls of osteopenia or rickets, while it has been seen that VDR at the level gonadal plays a role in the production of estrogen [ 27 , 28 ]. It has been showed that vitamin D regulates the biosynthesis of estrogens by means of calcitropic activity and by maintaining the homeostasis of intracellular and extracellular calcium in balance and by acting directly in the regulation of the expression of the aromatase gene [ 28 ]. The products of expression of the aromatase gene, such as Cytochrome P450 Family 19 Subfamily A Member 1 (CYP19A1) protein, an aromatase that plays a critical role in estrogen biosynthesis, thus, affects several organ-specific dysfunctions related to body fat distribution and to lipid metabolism regulations.…”

A Review: Cytochrome P450 in Alcoholic and Non-Alcoholic Fatty Liver Disease

“…90 Yang et al found that CYP19A1 upregulation promotes oestrogen production, attenuates IR via the transcription factor forkhead box o 1 (Foxo1), and inhibits lipid accumulation in the liver. 91 Evangelos et al reported that in an insulin resistant state, CYP7B1 stimulation leads to the advancement of steatohepatitis from simple steatohepatitis. 92 CYP4A and CYP4F play important roles in hepatic fatty acid metabolism.…”