No abstract

Recent animal studies have indicated that overexpression of the elongation of long-chain fatty acids family member 6 (Elovl6) gene can cause insulin resistance and β-cell dysfunction. These are the major factors involved in the development of type 2 diabetes mellitus (T2DM). To identify the relationship between single nucleotide polymorphisms (SNP) of ELOVL6 and T2DM pathogenesis, we conducted a case-control study of 610 Han Chinese individuals (328 newly diagnosed T2DM and 282 healthy subjects). Insulin resistance and islet first-phase secretion function were evaluated by assessment of insulin resistance in a homeostasis model (HOMA-IR) and an arginine stimulation test. Three SNPs of the ELOVL6 gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism, with DNA sequencing used to confirm the results. Only genotypes TT and CT of the ELOVL6 SNP rs12504538 were detected in the samples. Genotype CC was not observed. The T2DM group had a higher frequency of the C allele and the CT genotype than the control group. Subjects with the CT genotype had higher HOMA-IR values than those with the TT genotype. In addition, no statistical significance was observed between the genotype and allele frequencies of the control and T2DM groups for SNPs rs17041272 and rs6824447. The study indicated that the ELOVL6 gene polymorphism rs12504538 is associated with an increased risk of T2DM, because it causes an increase in insulin resistance.

The rs10983755, located in the 5'-untranslated region (UTR) of TLR4, was most strongly associated with FK of Chinese Han population (p < 0.05). The analysis of TLR2 gene polymorphisms showed no significant association upon FK susceptibilities of Chinese Han population.

Iron is essential for rapidly dividing spermatocytes during normal mammalian spermatogenesis. Decreased transferrin and transferrin receptor levels were observed in seminal plasma from idiopathic azoospermia (IA) patients, suggesting disturbed iron metabolism in IA testes. However, how Sertoli cells (SCs) contribute to the iron homoeostasis in IA is still unclear. In this study, we analysed 30 IA and 30 age-matched obstructive azoospermia (OA) patients undergoing testicular sperm aspiration (TESA). SCs hyperplasia was indicated by higher SC density and Ki-67 labelling index in the IA TESA specimens. The attenuated expression of superoxide dismutase (SOD) suggested an impaired antioxidative capacity in IA testes. We further detected increased levels of iron importer divalent metal transporter 1 with iron responsive element (DMT1 + IRE) in IA testes, whereas the increasing trend of iron exporter ferroportin 1 (FPN1) was not statistically significant. Next, we demonstrated that iron regulatory protein 1 (IRP1) and hypoxia-inducible factor-1α (HIF-1α), which can potentially bind to the IRE and hypoxia-responsive element in the DMT1 + IRE mRNA, were both up-regulated in IA testes. Unexpectedly, HIF-2α was down-regulated in IA testes. These results indicate that there is a dysregulation of DMT1 + IRE in IA testes, which might due to the up-regulation of IRP1 and HIF-1α.