SIRT6 reduces the symptoms of premature ovarian failure and alleviates oxidative stress and apoptosis in granulosa cells by degrading p66SHC via H3K9AC.

CONTEXT: Substantial evidence suggests that ovarian oxidative stress can result in severe ovarian dysfunction. OBJECTIVE: The purpose of this article is to investigate the potential of SIRT6 in alleviating premature ovarian failure (POF) by inhibiting oxidative stress. METHODS: To mimic POF, mice were administered daily subcutaneous injections of d-galactose. The levels of E2, FSH, LH, AMH, and progesterone in serum were measured, along with changes in follicles and SIRT6 levels. Mice were treated with the SIRT6 agonist MDL-800, SIRT6 levels, follicles, and aforementioned hormones were reassessed. The effects of MDL-800 on oxidative stress and apoptosis were subsequently identified. Primary granulosa cells were isolated from mice, and the effects of H2O2 and MDL-800 on cell viability, oxidative stress, SIRT6 level, and apoptosis were evaluated. In addition, the regulation of SIRT6 on H3K9AC/p66SHC was verified by examining changes in protein levels, promoter activity, and the reversal effects of p66SHC overexpression. RESULTS: MDL-800 mitigated hormone fluctuations, reduced follicle depletion in ovarian tissue, and attenuated oxidative stress and apoptosis in mice. In vitro experiments demonstrated that MDL-800 enhanced the resilience of primary granulosa cells against H2O2, as evidenced by increased cell viability and reduced oxidative stress and apoptosis. Furthermore, SIRT6 was found to decrease H3K9AC and p66SHC levels, as well as attenuate p66SHC promoter activity. The protective effects of MDL-800 on cells were reversed upon p66SHC overexpression. CONCLUSION: In summary, this study highlights that activation of SIRT6 can alleviate POF and reduce oxidative stress by degrading H3K9AC and suppressing p66Shc levels in granulosa cells.

Purinergic receptor P2X7 activates NOX2/JNK signaling to participate in granulosa cell inflammation and apoptosis in polycystic ovary syndrome.

Increasing evidence shows that polycystic ovary syndrome (PCOS) is often accompanied by an inflammatory response, hence, appropriately managing granulosa cell inflammation is critical to regaining ovarian function in PCOS. In this study, the differential levels of purinergic receptor P2X7 between the control and PCOS samples in the dataset GSE34526 were assessed, then PCOS mouse models were established. Following evaluating the fluctuations in hormone levels, inflammatory cytokines, and P2X7, mice received treatment with the P2X7 antagonist A740003. Its effects on hormones, inflammation, apoptosis, and NOX2 signaling in mice were examined. Afterward, primary mouse granulosa cells were isolated, and the mediating role of NOX2 signaling in the P2X7 regulatory pathway was confirmed by transfection of NOX2 overexpression plasmids. The results demonstrated that P2X7 was significantly elevated in the PCOS samples in the dataset. Compared with the control group, PCOS mice had significant differences in the follicle-stimulating hormone, luteinizing hormone, testosterone, anti-Müllerian hormone, inflammatory factors, and P2X7. Treatment with A740003 partially restored these parameter levels, including NOX2 signaling. Based on in vitro experiments on primary mouse granulosa cells, the above findings were re-verified, and the overexpression of NOX2 could reverse the regulatory function of P2X7. The present study highlights that P2X7 level increases in PCOS, and inhibition of P2X7 can reduce disease symptoms. It is involved in inflammation and apoptosis in granulosa cells through NOX2/JNK signaling.

Post-Traumatic Stress Disorder Is Associated with Elevated Plasma Cholesterol in Female TT Homozygotes of LDLR rs5925.

To explore the mechanism of inconsistent relationships between plasma lipid profiles and post-traumatic stress disorder (PTSD) reported before, we hypothesized that interplays might exist between PTSD and a variation of rs5925 at low-density lipoprotein receptor (LDLR) gene on plasma lipid profiles. To test our hypothesis, we analyzed the plasma lipid profiles of 709 high school pupils with various genotypes of LDLR rs5925 and with or without PTSD. The results demonstrated that PTSD prevalence in the C allele carriers was higher than that in the TT homozygotes regardless of gender. The C allele carriers had higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ratios of TC to high-density lipoprotein cholesterol (TC/HDL-C) and LDL-C/HDL-C than the TT homozygotes in the male controls, and only higher TC in the female controls, but no differences in the male or female PTSD subjects. PTSD increased TC in the female TT homozygotes but not in the female C allele carriers. PTSD increased TC/HDL-C in the male TT homozygotes but not in the C allele carriers. These results suggest interactions between PTSD and LDLR rs5925 on plasma lipid profiles, which may be among the explanations for previously reported inconsistent relationships between LDLR rs5925 or PTSD and plasma lipid profiles, and facilitate the development of precision medicine interferences in hypercholesterolemia in individuals with different genetic backgrounds and psychiatric status. Psychiatric care or drug supplement may particularly be needed by female hypercholesterolemic subjects with the TT genotype of LDLR rs5925 in Chinese adolescents.

PCSK9 rs7552841 is associated with plasma lipids profiles in female Chinese adolescents without posttraumatic stress disorder.

To explain the inconsistent relationship between proprotein convertase subtilisin/kexin type 9 (PCSK9) rs7552841 and plasma lipids profiles, we hypothesized that interplays might occur among gender, PCSK9 rs7552841 and posttraumatic stress disorder (PTSD) on plasma lipids levels. To test this hypothesis, a population of 704 Chinese Han high school students was used, which had been recruited after the 2008 Wenchuan Earthquake. In this population, the plasma levels of glucose, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) had been measured by routine methods. PTSD had been assessed by the PTSD Checklist Civilian Version (PCL-C). PCSK9 rs7552841 was analyzed by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. The T allele carriers had significantly higher levels of TG, TC, LDL-C, and glucose than the CC homozygotes of PCSK9 rs7552841 after the adjustment for age and BMI in the female students, but not in the male students. When PTSD was taken into consideration, the female T allele carriers had significantly higher TG, TC, LDL-C and glucose than the female CC homozygotes after the adjustment for age and BMI only in the subjects without PTSD, but not in the PTSD patients. No significant differences were observed in the male students regardless of PTSD and the adjustment for age and BMI. These results suggest that PCSK9 rs7552841 is associated with plasma lipids profiles only in female adolescents, but not in male students. This association can be modified and negated by PTSD.

Posttraumatic stress disorder eliminates association of TrkB rs1187327 with HDL-C in Chinese Han adolescents.

Tropomyosin-related kinase receptor B (TrkB) has been observed to be a common player in posttraumatic stress disorder (PTSD) and the regulation of serum lipids levels. However, interplays of PTSD with TrkB on serum lipids levels have not been explored yet. This study was to investigate the interplays of PTSD and TrkB rs1187327 on serum lipid profiles. Variants of TrkB rs1187327 of 709 high school students were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses and verified by DNA sequencing. The PTSD Checklist Civilian Version (PCL-C) was used to assess PTSD. Colorimetric methods were used to determine the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and glucose. The results show that the GG homozygotes had a significantly higher level of HDL-C than the A allele carriers of TrkB rs1187327 after the adjustment for gender, age and body mass index (BMI) (1.44 ± 0.299 mmol/L vs. 1.39 ± 0.266 mmol/L, p = 0.036). When PTSD was taken into account, the higher than the A allele carriers level of HDL-C of the GG homozygotes was observed significant after the adjustment for gender, age and BMI only in the subjects without PTSD (1.44 ± 0.293 mmol/ L vs. 1.39 ± 0.267 mmol/L, p = 0.030), but not in the subjects with PTSD. These results suggest that the A allele of TrkB rs1187327 may be associated with decreased levels of serum HDL-C in general healthy adolescents, but not in adolescents with PTSD.

Predictive factors of depression symptoms among adolescents in the 18-month follow-up after Wenchuan earthquake in China.

BACKGROUND: It is unclear about the change and risk factors of depression among adolescent survivors after earthquake. AIMS: This study aimed to explore the change of depression, and identify the predictive factors of depression among adolescent survivors after the 2008 Wenchuan earthquake in China. METHODS: The depression among high school students at 6, 12 and 18 months after the Wenchuan earthquake were investigated. The Beck Depression Inventory (BDI) was used in this study to assess the severity of depression. RESULTS: Subjects included 548 student survivors in an affected high school. The rates of depression among the adolescent survivors at 6-, 12- and 18-month after the earthquake were 27.3%, 42.9% and 33.3%, respectively, for males, and 42.9%, 61.9% and 53.4%, respectively, for females. Depression symptoms, trauma-related self-injury, suicidal ideation and PTSD symptoms at the 6-month follow-up were significant predictive factors for depression at the 18-month time interval following the earthquake. CONCLUSIONS: This study highlights the need for considering disaster-related psychological sequela and risk factors of depression symptoms in the planning and implementation of mental health services. Long-term mental and psychological supports for victims of natural disasters are imperative.

p53 increase mitochondrial copy number via up-regulation of mitochondrial transcription factor A in colorectal cancer.

In colorectal cancer, no study has been carried out discovering the relationship among p53, mitochondrial transcription factor A (TFAM) expression and change of mitochondrial DNA (mtDNA) copy number. In our study, co-expression of p53 and TFAM was observed in colon adenocarcinoma tissues, paracancerous tissues and 9 colorectal cancer cell lines. Then, a significant linear correlation was established between either p53 or TFAM expression and advanced TNM stage, positive lymph nodes and low 5-year survival rate in patients with colon adenocarcinoma. Additionally, advanced TNM stage, large tumor burden, presence of distant metastasis, and high TFAM expression were significantly related to poor overall 5-years survival. Moreover, alteration of p53 expression could change TFAM expression but TFAM could not influence p53 expression, and p53 could enhance TFAM expression via binding to TFAM promoter. While, both of p53 and TFAM expression could incrase mtDNA copy number in vitro. In conclusions, p53 might incrase mtDNA copy number through its regulation on TFAM expression via TFAMpromoter.

Association of 25-hydroxyvitamin D status with obesity as well as blood glucose and lipid concentrations in children and adolescents in China.

BACKGROUND: Vitamin D is an essential micronutrient during the growth and development of the human body. Previously, most of the researches about the relationship of vitamin D and obesity were focused on adults. In this paper, the relationship between serum 25-hydroxyvitamin D [25(OH)D] and obesity among children and adolescents in China was analyzed. METHODS: From August 2012 to August 2014, 443 children and adolescents participated in this study. Serum 25(OH)D, lipid and glucose were measured in the laboratory. All the participants were classified into 2 groups (obese and non-obese group) on the basis of their BMI. They were then categorized into vitamin D deficiency, vitamin D insufficiency and vitamin D normal groups according to the serum concentrations of 25(OH)D. RESULTS: The concentration of serum 25(OH)D in the obese group was significantly lower than that of the non-obese group (P<0.001). The concentration of total cholesterol, low-density lipoprotein cholesterol, fasting blood glucose, fasting insulin and homeostasis model assessment for insulin resistance showed significant differences between the obese and non-obese groups (P<0.05). CONCLUSIONS: Children and adolescents suffering from obesity are more likely to have lower concentrations of serum 25(OH)D.

Association of Leptin Receptor Gene Polymorphisms with Genetic Susceptibility to Ischemic Stroke.

BACKGROUND: Ischemic stroke is a multifactorial disease that is influenced by both genetic and environmental factors. Identification of the genetic factors that are underlining this disease is important. Leptin receptor (LEPR) mediates the leptin-regulated human energy homeostasis, and mutations of LEPR can increase cardiovascular risks and may predispose an individual to ischemic stroke. METHODS: We analyzed distribution of 3 single nucleotide polymorphisms (SNPs) of LEPR gene (Lys109Arg, Gln223Arg, and Lys656Asn) in 101 patients with ischemic stroke and 105 controls by polymerase chain reaction-restriction fragment length polymorphism strategy. RESULTS: Our results showed that there were significant differences in the genotype and allele distribution of Lys109Arg and Gln223Arg polymorphisms of the LEPR gene between case and control. The 109GG and 223GG genotype were associated with a significantly increased risk of ischemic stroke (odds ratio [OR], 3.23; P = .001 and OR, 2.87; P = .008, respectively). The 109G and 223G alleles carriers were correlated with an increased incidence of ischemic stroke (OR, 2.72; P = .001; OR, 2.94; P = .004). By haplotype analyses, we found that 109A/223G/656G haplotype was associated with an increased risk of ischemic stroke although this was not observed in the control group (OR, 3.86; P = .029). CONCLUSIONS: LEPR 109GG and 223GG genotypes and the 109G and 223G alleles are associated with the risk of ischemic stroke. Our data suggest that LEPR Lys109Arg and Gln223Arg polymorphisms could be used as genetic predictive factor for ischemic stroke.

Risk factors of suicidal ideation among adolescents after Wenchuan earthquake in China.

BACKGROUND: Suicidal ideation is a common phenomenon in survivors after disaster event. AIM: To identify the change of suicidal ideation, and to test hypotheses concerning the suicidal ideation, depression and PTSD symptoms among adolescent survivors after the 2008 Wenchuan earthquake in China. METHODS: The suicidal ideation among high school students at 6, 12 and 18 months after the Wenchuan earthquake were investigated. Subjects included 737 student survivors in an affected high school. The PTSD Checklist-Civilian Version (PCL-C) and the Chinese Beck Depression Inventory (C-BDI) were used to measure the symptoms of PTSD and depression. RESULTS: The rates of suicidal ideation among the adolescent survivors at 6-, 12- and 18-month after the earthquake were 35.6%, 35.6% and 30.7% respectively. Depression symptoms in the 18-month follow-up, suicidal ideations at 6 and 12 months after the earthquake were the independent risk factors of suicidal ideation in the 18-month follow-up. Depression symptoms were the strongest predictor of suicidal ideation after earthquake. CONCLUSION: An increased rate of suicidal ideation after the earthquake may be mainly due to depression but not to PTSD symptoms. The disaster-related psychological sequelae and the risk factors of suicidal ideation, especially depression symptoms, should be considered in the mental health services and suicide prevention.

[Effects of APOC3 polymorphisms on the plasma lipids in healthy adolescents with different body mass index].

OBJECTIVE: To investigate the possible effects of apolipoprotein C I gene (APOC3) polymorphisms on plasma lipids in healthy adolescents with different body mass index (BMI). METHODS: Seven hundred and twenty three adolescents were divided into four groups according to BMI: group 1 CBMI= (17.80 +/- 0.75) kg/m2,n=180], group 2 [BMI = (19.39 +/- 0.32) kg/m2, n=182), group 3 [BMI= (20.68 +/- 0.43) kg/m2, n=1813 and group 4 [BMI= (23.40 +/- 2.05) kg/m2 ,n=180J. Fasting venous blood samples were collected, plasma lipids were determined and genome DNA was extracted for determining the genotypes of the APOC3 Sst I and -482C>T polymorphisms by PCR-RFLP. RESULTS: With the elevation of BMI, height and plasma high-density lipoprotein cholesterol decreased significantly (P<0.001 for both), body mass, waist circumference, hip circumference, waist/hip ratio, plasma triglycerides (TG), total cholesterol and low-density lipoprotein cholesterol levels increased significantly (P<0.001 for all). No significant differences in TG levels among Sst I genotypes were observed in group 1, group 2 and group 3; but in group 4, significant differences in TG levels among Sst I genotypes were observed, S2 carriers had higher TG levels than the adolescents with S1S1 genotype. No significant differences in plasma lipids among -482C>T genotypes were observed in all groups. CONCLUSION: The elevation of plasma TG levels by the S2 allele of APOC3 Sst I polymorphism is associated with BMI. It is possible that the reduction of body mass could favorably modulate the elevation of TG levels by S2 allele in healthy adolescents.

[Effects of apolipoprotein A1 gene rs670 and rs5069 polymorphisms on the plasma lipid profiles in healthy adolescents with different body mass index].

OBJECTIVE: To investigate the possible effects of apolipoprotein A1 gene (APOA1) rs670 and rs5069 polymorphisms on plasma lipid profiles in healthy adolescents with different body mass index (BMI). METHODS: Totally 723 adolescents were divided into four groups according to their BMI: group 1[BMI =(17.80 ± 0.75)kg/m2], group 2[BMI = (19.39 ± 0.32) kg/m²], group 3[BMI = (20.68 ± 0.43) kg/m²], and group 4[BMI=(23.40 ± 2.05) kg/m²]. Height, weight, waist circumference, hip circumference, blood pressure, heart rate, plasma lipids, and blood glucose were determined, BMI and waist to hip ratio (W/H ratio) were calculated,and genome DNA was extracted for analyzing the genotypes of the APOA1 rs670 and rs5069 polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No significant differences in height, weight, BMI, waist circumference, hip circumference, W/H ratio, blood pressure, heart rate, plasma lipids, and blood glucose between APOA1 rs670 or rs5069 genotypes were observed among group 1, group 2, and group 3. In group 4, A carriers of the rs670 polymorphism had significantly higher systolic blood pressure (P=0.017) and blood glucose levels (P=0.009) than the adolescents with the GG genotype. T carriers of the rs5069 polymorphism had significantly higher height (P=0.013), weight (P=0.011), and hip circumference (P=0.026) than the adolescents with the CC genotype. CONCLUSIONS: In healthy adolescents with higher BMI, APOA1 rs670 polymorphism is associated with systolic blood pressure and blood glucose levels. The elevation of systolic blood pressure and blood glucose levels in A carriers of APOA1 rs670 polymorphism may be favorably modulated by weight loss.

A high-carbohydrate diet lowered blood pressure in healthy Chinese male adolescents.

Different diets consumed by individuals of different ethnicities, gender, and age may cause changes in blood pressure. The current study sought to investigate changes in blood pressures after consumption of a high-carbohydrate (high-CHO) diet by healthy Chinese adolescents. As a population, the Chinese consume a diet with a high carbohydrate content and they have a low incidence of hypertension and coronary artery disease. Dietary data were collected using a 3-day diet diary. Subjects were 672 high school students who were divided into a high-CHO diet group (≥ 55% carbohydrates) and a non-high-CHO diet group (< 55% carbohydrates, < 40% fats). Plasma glucose levels, heart rate, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured. Body mass index (BMI), waist-to-hip ratio (WHR), pulse pressure (PP), and mean arterial pressure (MAP) were calculated. Results indicated that males had a higher BMI, glucose level, SBP, DBP, PP, and MAP than females. When diet was taken into account, males in the non-high-CHO diet group had a higher SBP and PP than females. Males in the high-CHO diet group had a higher glucose level than females. Males in the high-CHO diet group had a lower SBP (p = 0.004) and PP (p = 0.002) than males in the non-high-CHO diet group and females in the high-CHO diet group had a lower glucose level (p = 0.003) than females in the non-high-CHO diet group. After adjusting for age, BMI, WHR, heart rate, the total daily energy intake, and the intake of vitamin C, calcium, sodium, potassium and magnesium, significant differences in SBP and PP were noted in males. These results indicate that male adolescents consuming a high-CHO diet had a lower SBP and PP than males consuming a non-high-CHO diet.

Associations of lipoprotein lipase gene rs326 with changes of lipid profiles after a high-carbohydrate and low-fat diet in healthy Chinese Han youth.

To investigate the effects of a high-carbohydrate and low-fat (HC/LF) diet on plasma lipids and apolipoproteins (Apos) of healthy Chinese Han youth with different genotypes of lipoprotein lipase gene (LPL) rs326, 56 subjects were given a washout diet of 30.1% fat and 54.1% carbohydrate for seven days, followed by the HC/LF diet of 13.8% fat and 70.1% carbohydrate for six days, with no total energy restriction. Plasma glucose, triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), Apo B-100 and Apo A-I were analyzed at baseline and before and after the HC/LF diet. The results show that, when compared with before the HC/LF diet, only the male G carriers experienced increased HDL-C (p = 0.008) and Apo A-I (p = 0.005) after the HC/LF diet. Decreased TC in both males and females and increased TG in females were found regardless of the genotype after the HC/LF diet. LDL-C decreased in all the subjects although the decrease was not significant in the female G carriers. These results demonstrate that the G allele of LPL rs326 associates with the elevated levels of HDL-C and Apo A-I after the HC/LF diet in males of the healthy Chinese Han Youth.

The supercritical CO2 extract from the skin of Bufo bufo gargarizans Cantor blocks hepatitis B virus antigen secretion in HepG2.2.15 cells.

The skin of Bufo bufo gargarizans Cantor has long been used for the treatment of hepatitis B in China and supercritical carbon dioxide extraction (SC-CO2) is widely used in extracting active ingredients from natural products. The aim of present study was to assess the anti-hepatitis B virus (HBV) effect of the supercritical CO2 extract from the skin of Bufo bufo gargarizans Cantor (SCE-BC). Cytotoxicity of SCE-BC was analyzed using an MTT [3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide] assay in HepG2.2.15 cells. The hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core-related antigen (HBcrAg) concentrations in cell culture medium were determined by chemiluminescent enzyme immunoassay. HBV mRNA in cells was determined using real-time polymerase chain reaction. SCE-BC concentrations below 10(-2) µg/mL had no significant toxicity to HepG2.2.15 cells. SCE-BC at 10(-4) µg/mL effectively inhibited the secretion of HBeAg by 23.36% on day 6. It was more potent than the positive control lamivudine (100 µg/mL) in terms of the inhibition of HBeAg and HBcrAg secretion on day 6. Consistent with the HBV antigen reduction, HBV mRNA expression was markedly inhibited in comparison to the control when HepG2.2.15 cells were treated with SCE-BC. Moreover, SCE-BC had greater inhibitory activity with respect to HBeAg than to HBsAg. Since HBeAg promotes immune tolerance and persistent infection during HBV infection, the present results suggest that immune tolerance induced by HBeAg might be overcome by SCE-BC. Therefore, SCE-BC warrants further investigation.

[The association study of the LIPC -250g/A polymorphism and high-carbohydrate/low-fat diet induced serum lipid and apolipoprotein concentration changes in healthy youth].

OBJECTIVE: To investigate the role of the - 250G/A polymorphism in the promoter region of hepatic lipase gene (LIPC) on serum lipid profile and its interactions with a high-carbohydrate/low-fat (HC/LF) diet on serum lipid profiles in a young healthy Chinese population. METHODS: After a stabilization diet for seven days, fifty-six young healthy subjects (27 males, 29 females) were given the HC/LF diet for six days. The serum lipid profiles were analyzed of the twelve-hour fasting venous blood samples collected in the mornings of the first, the eighth and the fourteenth days. The concentrations of serum apolipoproteins were measured. The LIPC -250G/A polymorphism were analyzed. RESULTS: At baseline, the female subjects with the GG genotype had significantly higher high-density lipoprotein cholesterol (HDL-C) (P= 0. 041) and apolipoprotein A- I (Apo A- I ) (P= 0. 020) than the male subjects with the same genotype. After the stabilization diet, the females had significantly higher HDL-C (GG genotype: P=0. 021, A carriers: P=0. 014) and Apo A-I (GG genotype: P= 0. 035, A carriers: P= 0. 006) than the males in all genotypes. After the HC/LF diet, the female A carriers had significantly higher total cholesterol (TC) (P= 0. 042) than the male A carriers, and the females had significantly higher Apo A- I than the males in all genotypes (GG genotype: P=0. 010, A carriers: P=0. 009). Compared with thosebefore the HC / LF diet , TC ( males with GG genotype : P = 0. 013 , male A carriers: P = 0. 000 ; females with GG genotype: P=0. 025, female A carriers: P=0. 048) and low-density lipoprotein cholesterol (LDL-C) (males with GG genotype: P = 0. 028, male A carriers: P = 0. 000; females with GG genotype: P= 0. 004, female A carriers: P=0. 001) significantly decreased after the diet in all the subjects. Triglycerides (TAG) (GG genotype: P=0. 006, A carriers: P= 0. 001) significantly increased in the females regardless of the genotype. However, only in the male A carriers, HDL-C (P= 0. 011) and Apo A- I (P= 0. 041) significantly increased after the diet. CONCLUSION: The A allele at the LIPC -250G/A polymorphism is associated with the HC/LF diet induced HDL-C and Apo A-I concentration changes in the males.

[Effects of an insertion/deletion polymorphism of angiotensin converting enzyme gene on the changes of serum lipid ratios and blood pressure induced by a high-carbohydrate and low-fat diet].

OBJECTIVE: To investigate the effects of an insertion/deletion (I/D) polymorphism at the intron 16 of the gene of angiotensin converting enzyme (ACE) on the changes of serum lipid ratios and blood pressure induced by a high-carbohydrate and low-fat (HC/LF) diet in healthy Chinese Han youth. METHODS: Fifty six healthy Chinese Han young volunteers were enrolled. A washout diet was given for seven days followed by the HC/LF diet for six days. Serum lipids and blood pressure were measured on the 1st, 8th, and 14th days. Serum lipid ratios were calculated. The ACE I/D polymorphism was detected by PCR. RESULTS: There were no significant differences of serum lipid ratios and blood pressure at baseline and before and after the HC/LF diet between the II genotype and the D carriers (ID and DD genotypes) in the whole study population, the males or the females separately. When compared with those before the HC/LF diet, all the subjects regardless of the genotype experienced statistical decreases of low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL-C/HDL-C) and total cholesterol (TC)/HDL-C, but significant decrease of systolic blood pressure (SBP) was only found in the subjects with the II genotype. After taking into account gender, triglyceride (TG)/HDL-C and Log (TG/HDL-C) decreased in the males with theII genotype and increased in the female counterparts. The decreases of TC/HDL-C and LDL-C/HDIL-C were observed in all the males and the female D carriers. SBP decreased only in the male D carriers. CONCLUSION: The interaction of the HC/LF diet with the I allele of the intron 16 I/D polymorphism at the ACE gene decreases TG/HDL-C and log (TG/HDL-C) in males, but increases TG/HDL-C and log (TG/HDL-C) in females in the Chinese young population. The interplay with the D allele lowers SBP in males, and TC/HDL-C and LDL-C/ HDL-C in females.

[The role of CD14 promoter - 159 C-> T polymorphism on changes of serum lipid ratios induced by high-carbohydrate/low-fat diets in healthy Chinese Han youth].

OBJECTIVE: To investigate the role of CD14 promoter - 159 C-> T polymorphism on ratios of serum lipids and its interaction on the ratios with a high-carbohydrate/low-fat (HC/LF) diet in a young and healthy Chinese Han population. METHODS: After a washout diet for seven days, fifty six healthy young subjects (22.89 +/- 1.80 years) were given the HC/LF diet for six days. Twelve-hour fasting venous blood samples were collected in the mornings of the first, the eighth and the fourteenth days. The serum lipid profiles and the CD14 -159 C->T polymorphism were analyzed. The ratios of triglyceride/high density lipoprotein-cholesterol (TG/HDL-c), log (TG/HDL-c), total cholesterol/high density lipoprotein-cholesterol (TC/HDL-c) and low density lipoprotein-cholesterol/high density lipoprotein-cholesterol (LDL-c/HDL-c) were calculated. RESULTS: The male carriers of the C allele had significantly higher TG/HDL-c and log (TG/HDL-c) than the female carriers at baseline, after the washout diet and after the HC/LF diet, higher TC/HDL-c at baseline and after the washout diet, and higher LDL-c/HDL-c only after the washout diet. The female subjects with the TT genotype had higher TG/HDL-c and log (TG/HDL-c) than the female carriers of the C allele at baseline, after the washout diet and after the HC/LF diet, higher LDL-c/HDL-c at baseline and after the HC/LF diet, and higher TC/HDL-c only after the washout diet. Compared with that before the HC/LF diet, TC/HDL-c was significantly decreased after the HC/LF diet regardless of gender and the genotype of the CD14 -159 polymorphism. LDL-c/HDL-c was significantly decreased in both the male and female carriers of the C allele. TG/HDL-c and log (TG/HDL-c) were significantly increased only in the female carriers of the C allele. CONCLUSION: In the subjects with C allele, the HC/LF diet is a minor factor and its effects on the lipid ratios can be masked by the effects of the C allele at CD14 -159. The interaction between the HC/LF diet and the C allele at CD14 -159 can decrease LDL-c/HDL-c in both males and females and increase TG/ HDL-c and log (TG/HDL-c) in the females.

[Effects of a high-carbohydrate diet on the serum lipid and apolipoprotein ratios in healthy young adults with different genotypes of APOA1 -75 G/A polymorphism].

OBJECTIVE: To investigate the effects of a high-carbohydrate diet on the lipid and apolipoprotein ratios in healthy young adults with different genotypes of the polymorphism at -75 site in the promoter region of the gene of apolipoprotein AI (APOA1). METHODS: Fifty-six subjects aged (22.89 +/- 1.80) years were given a wash-out diet for 7 days, followed by a high-carbohydrate diet for 6 days. The wash-out diet contained 15% protein, 31% fat, and 54% carbohydrate. The high-carbohydrate diet contained 15% protein, 15% fat, and 70% carbohydrate. Twelve-hour fasting serum lipids and apolipoproteins B100 and AI were measured on the mornings of the 1st, the 8th, and the 14th days from the beginning of the wash-out diet. The ratios of triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC)/HDL-C, low-density lipoprotein cholesterol (LDL-C)/HDL-C, and apolipoprotein B100 (APOB100)/apolipoprotein AI (APOAI) were calculated. The genome DNA was extracted and the polymorphism of APOA1 -75 G/A was determined by polymerase chain reaction followed by restriction fragment length polymorphism assay. RESULTS: At baseline, the lipid and apolipoprotein ratios showed no significant differences between the GG genotype and the A carriers in males (P > 0.05), whereas the female A carriers had a significantly higher ratio of LDL-C/ HDL-C compared with the female subjects with the GG genotype (P < 0.05). Following the high-carbohydrate diet, significant decreases of TC/HDL-C were found in all the groups, regardless of sex and genotype (P < 0.01). LDL-C/HDL-C experienced significant decreases in both the genotypes in males (P < 0.05), while in females, significant decrease of LDL-C/HDL-C was only observed in A carriers (P < 0.01). CONCLUSION: The A allele of the -75 G/A polymorphism in APOA1 may have specific effects on the LDL-C/HDL-C ratio in females.