[AGT rs5051 gene polymorphism increases the risk of coronary heart disease in patients with non-alcoholic fatty liver disease in the Han Chinese population].

Objective: To investigate the relationship between the angiotensinogen (AGT) rs5051 single nucleotide polymorphism (SNP) and the onset risk of coronary heart disease (CHD) in patients with non-alcoholic fatty liver disease (NAFLD) in the Han Chinese population. Methods: A total of 454 subjects were enrolled in this study. Among them, 140 cases were with NAFLD, 112 cases with NAFLD combined with CHD, and 202 healthy controls. Blood samples of all subjects were examined for biochemical indexes. Genotype at AGT rs5051 locus was detected by polymerase chain reaction. SPSS 21.0 statistical software was used for data statistical analysis. Results: The differences in distribution of AGT rs5051 genotypes and alleles between the NAFLD and the control group were not statistically significant (P > 0.05). The differences in the distribution of AGT rs5051 genotypes and alleles between the NAFLD combined with CHD and the NAFLD group were statistically significant (χ(2) = 10.32, P = 0.001; χ(2) = 11.72, P < 0.001). Binary logistic regression analysis results showed that TC + CC genotype had increased the occurrence risk of CHD in NAFLD patients (OR = 2.203, 95% CI: 1.322 ~ 3.670, P = 0.02) than AGT rs5051 TT genotype carriers. After adjusting for gender, age, and body mass index, the TC + CC genotype still significantly increased the occurrence risk of CHD in NAFLD patients (OR = 2.378, 95% CI: 1.384 ~ 4.087, P = 0.02). In addition, AGT rs5051 C allele mutations had significantly increased the occurrence risk of CHD in patients with NAFLD (OR = 2.018 before adjustment, 95% CI: 1.345 ~ 3.027, P = 0.001; OR = 2.161, 95% CI: 1.406 ~ 3.322 after adjustment. P < 0.001). Conclusion: This study is the first to report the correlation between AGT rs5051 polymorphism and the occurrence risk of CHD in patients with NAFLD in Han Chinese population. AGT rs5051 polymorphism can significantly increase the risk of CHD in patients with NAFLD.

Oligoasthenoteratospermia and sperm tail bending in PPP4C-deficient mice.

Protein phosphatase 4 (PPP4) is a protein phosphatase that, although highly expressed in the testis, currently has an unclear physiological role in this tissue. Here, we show that deletion of PPP4 catalytic subunit gene Ppp4c in the mouse causes male-specific infertility. Loss of PPP4C, when assessed by light microscopy, did not obviously affect many aspects of the morphology of spermatogenesis, including acrosome formation, nuclear condensation and elongation, mitochondrial sheaths arrangement and '9 + 2' flagellar structure assembly. However, the PPP4C mutant had sperm tail bending defects (head-bent-back), low sperm count, poor sperm motility and had cytoplasmic remnants attached to the middle piece of the tail. The cytoplasmic remnants were further investigated by transmission electron microscopy to reveal that a defect in cytoplasm removal appeared to play a significant role in the observed spermiogenesis failure and resulting male infertility. A lack of PPP4 during spermatogenesis causes defects that are reminiscent of oligoasthenoteratospermia (OAT), which is a common cause of male infertility in humans. Like the lack of functional PPP4 in the mouse model, OAT is characterized by abnormal sperm morphology, low sperm count and poor sperm motility. Although the causes of OAT are probably heterogeneous, including mutation of various genes and environmentally induced defects, the detailed molecular mechanism(s) has remained unclear. Our discovery that the PPP4C-deficient mouse model shares features with human OAT might offer a useful model for further studies of this currently poorly understood disorder.