Effect of the beta-3 adrenergic receptor Trp64Arg and uncoupling protein 1-3826 A>G genotypes on lipid and apolipoprotein levels in overweight/obese and non-obese Chinese subjects.

BACKGROUND: The beta-3 adrenergic receptor (ß3-AR) Trp64Arg and uncoupling protein 1 (UCP1) -3826 A>G polymorphisms have been reported to be associated with obesity and/or lipid metabolism in some populations. This study examined the possible association of the ß3-AR and UCP1 polymorphisms with overweight/obesity or lipid variation in a Southwest Chinese population. METHODS: A total of 418 Han Chinese (249 overweight/obese and 169 healthy control subjects) in the Chengdu area were studied using PCR-RFLP analysis. Total serum cholesterol (TC) and triglycerides (TGs) were measured using an enzymatic method. High density lipoprotein cholesterol (HDL-C) was determined after sodium phosphotungstate/magnesium chloride precipitation of low-density lipoproteins by polyvinyl sulfate. Serum apolipoproteins were quantified by radial immunodiffusion. RESULTS: The genotype and allele frequencies of the ß3-AR Trp64Arg and UCP1 -3826 A>G polymorphisms in overweight/obese subjects exhibited no significant differences compared to the controls. However, subjects carrying the ß3-AR TrpTrp genotype and UCP1 AG genotype had higher TG levels than those carrying the Arg allele and AA genotype, respectively (P<0.05), while controls carrying the ß3-AR Arg allele had significantly higher TC and apo AII concentrations than those carrying the TrpTrp genotype (P<0.05). Additionally, subjects carrying the UCP1 AG genotype exhibited elevated apo C-II and apo C-III levels compared to those carrying the AA genotype (P<0.05). We were unable to find an association of the UCP1 and ß3-AR polymorphisms with low HDL-cholesterolemia in the overweight/obese subjects. CONCLUSIONS: The present study provides evidence that the ß3-AR Trp64Arg and UCP1 -3826 A>G polymorphisms are associated with TG levels in overweight/obese Chinese subjects and that the two polymorphisms are also associated with certain lipid and apolipoprotein variations, depending on BMI. However, these polymorphisms are not associated with overweight/obesity or low HDL-cholesterolemia in a Chinese population from the Chengdu area.

[Association study between -765G > C and -1195G > A functional polymorphisms in the cyclooxygenase 2 gene and risk of preeclampsia].

OBJECTIVE: To investigate the relationship between two polymorphisms immediately upstream of the cyclooxygenase 2 (COX2) gene and preeclampsia in a South West Han Chinese population. METHODS: Blood samples from 205 patients with preeclampsia and 276 normal pregnant women as controls from Han Chinese in Chengdu area were analyzed by polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: G and A allele frequencies for -1195G>A site were 48.54% and 51.46% in the patient group, respectively, and 40.40% and 59.60% in the control group, respectively. G and C allele frequencies for -765G>C site were 94.15% and 5.85% in the case group, respectively, and 94.38% and 5.62% in the control group, respectively. The AA genotype and variant A allelic frequencies of the -1195G>A SNP were significantly lower in patients with preeclampsia than in the control group (P<0.05), and the odds ratio for the risk of preeclampsia was 0.665 (95% CI: 0.444-0.982) in women homozygous for the variant COX2 A allele ( x²=4.233, P=0.047). The genotype and allele frequencies of the -765G>C polymorphism in patients with preeclampsia and controls showed no significant differences (P>0.05). Additional subgroup analyses (mild vs severe preeclampsia) of the two polymorphisms failed to reveal significant correlation for either genotypic or allelic frequencies. Furthermore, there was no significant association between the polymorphisms and blood pressure levels in the patient or control groups. CONCLUSION: COX2 -1195A homozygosity is associated with a decreased risk for preeclampsia in a South West Han Chinese population. On the other hand, the -765G>C polymorphism has no effect.

[Interaction between GNB3 C825T and ACE I/D polymorphisms in pre-eclampsia].

OBJECTIVE: To verify the hypothesis if interaction between the G protein beta3 subunit (GNB3) C825T polymorphism and angiotensin-I converting enzyme (ACE) insertion/deletion (I/D) could lead to the increased risk of pre-eclampsia. METHODS: Analyses of ACE and GNB3 genotypes were performed in 188 preeclamptic patients and 273 normal pregnant controls by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism in Chinese population, respectively. RESULTS: The distributions of alleles and genotypes for the GNB3 C825T and ACE I/D polymorphisms were not found to be significantly associathed with pre-eclamptic status. No significant interaction of the influence of GNB3 T allele and ACE genotypes on the risk of pre-eclampsia was observed (OR 0.439-1.203, all P>0.05). However, we found that in homozygous 825T genotype carriers with the ACE II genotype in controls diastolic blood pressure (DBP) levels showed highest [(77.61 +/- 1.26) mmHg (1 mmHg=0.133 kPa)] among other three genotype combinations [TT/ID, (70.94 +/- 1.64) mmHg; CT/ID, (73.15 +/- 0.89) mmHg; CT/DD, (72.57 +/- 2.14) mmHg] (all P<0.05). No significant effect on systolic blood pressure (SBP) or DBP levels in the patients were observed. CONCLUSION: Our data suggest no significant interaction of the GNB3 825T allele carriers with the ACE I/D polymorphism in pre-eclampsia in Chinese population in Chengdu area. However there is the interaction of the two genes on DBP levels in pregnancy women without pre-eclampsia in the population.

A small physiological electric field mediated responses of extravillous trophoblasts derived from HTR8/SVneo cells: involvement of activation of focal adhesion kinase signaling.

Moderate invasion of trophoblast cells into endometrium is essential for the placental development and normal pregnancy. Electric field (EF)-induced effects on cellular behaviors have been observed in many cell types. This study was to investigate the effect of physiological direct current EF (dc EF) on cellular responses such as elongation, orientation and motility of trophoblast cells. Immortalized first trimester extravillous trophoblast cells (HTR-8/SVneo) were exposed to the dc EF at physiological magnitude. Cell images were recorded and analyzed by image analyzer. Cell lysates were used to detect protein expression by Western blot. Cultured in the dc EFs the cells showed elongation, orientation and enhanced migration rate compared with non-EF stimulated cells at field strengths of 100 mV/mm to 200 mV/mm. EF exposure increased focal adhesion kinase (FAK) phosphorylation in a time-dependent manner and increased expression levels of MMP-2. Pharmacological inhibition of FAK impaired the EF-induced responses including motility and abrogated the elevation of MMP-2 expression. However, the expression levels of integrins like integrin α1, α5, αV and ß1 were not affected by EF stimulation. Our results demonstrate the importance of FAK activation in migration/motility of trophobalst cells driven by EFs. In addition, it raises the feasibility of using applied EFs to promote placentation through effects on trophoblast cells.