PCMT1 gene polymorphisms, maternal folate metabolism, and neural tube defects: a case–control study in a population with relatively low folate intake

The PCMT1 gene encodes the protein repair enzyme protein-l-isoaspartate (d-aspartate) O-methyltransferase, which is known to protect certain neural cells against Bax-induced apoptosis. Previous studies have produced inconsistent results regarding the effects of PCMT1 (rs4816 and rs4552) polymorphisms on neural tube defects (NTDs). Reduced maternal plasma folate levels and/or elevated homocysteine (Hcy) levels are considered to be risk factors for NTDs. In order to clarify the key factors contributing to the apparent discrepancy and investigate gene–environment interaction, we conducted a case–control study including 121 cases and 146 matched controls to investigate the association between the two PCMT1 polymorphisms in fetuses and the risk of NTDs in the Chinese population of Lvliang, which has low folate intake. Maternal plasma folate and Hcy levels were also measured, and the interaction between fetal PCMT1 gene status and maternal folate metabolites was assessed. Maternal plasma folate concentrations in the NTD group were lower than in controls (10.23 vs. 13.08 nmol/L, adjusted P = 0.059), and Hcy concentrations were significantly higher (14.46 vs. 11.65 μmol/L, adjusted P = 0.026). Fetuses carrying the rs4816 AG + GG genotype, combined with higher maternal plasma Hcy, had a 6.46-fold (95 % CI 1.15–36.46) increased risk of anencephaly. The results of this study imply that the fetal PCMT1 rs4816 polymorphism may play only a weak role in NTD formation and that gene–environment interactions might be more significant.     

PPARγ2 Pro12Ala polymorphism is associated with improved lipoprotein lipase functioning in adipose tissue of insulin resistant obese women

Lipoprotein lipase (LPL) plays a pivotal role in lipid metabolism, contributes to metabolic disorders related to insulin action and body weight regulation, and is influenced by inflammation. The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPAR)γ2 gene seems to influence LPL functioning, but its role in obesity and insulin resistance status, which usually coexist in the clinical setting, has not been explored. Our aim was to analyze the association of obesity and insulin resistance with adipose LPL activity and expression, and the influence of the PPARγ2 Pro12Ala polymorphism. A cross-sectional study was conducted in 58 reproductive-age women who underwent elective abdominal surgery. Free-fatty acids, glucose, insulin, and selected adipokines were measured in fasting blood samples. DNA was isolated and the polymorphism genotyped. Biopsies of abdominal subcutaneous adipose tissue obtained during surgery were used to determine enzymatic LPL activity and expression; and expression of selected cytokines. Overweight/obese women presented lower LPL activity (P = 0.022) and higher circulating TNF-α (P = 0.020) than controls. Insulin resistant women also showed borderline lower LPL activity than non-resistant (P = 0.052), but adiposity and inflammatory molecules were comparable. Nevertheless, LPL activity was higher in Pro12Ala carriers than in non-carriers after adjusting for obesity, insulin resistance and inflammation. Likewise, adipose LPL expression was increased in carriers while expression of cytokines was decreased. Our data suggest that insulin resistance is associated with low adipose LPL activity independently of obesity, but the PPARγ2 Pro12Ala polymorphism seems to protect the LPL functioning of obese insulin resistant women, likely through regulating inflammation in adipose tissue.     

TaqIB polymorphism in the CETP gene modulates the impact of HC/LF diet on the HDL profile in healthy Chinese young adults

The aim of this study was to investigate the interactions of genetic variants in the genes of cholesterol ester transfer protein (CETP) and low-density lipoprotein receptor (LDLR) with high carbohydrate and low fat (HC/LF) diet on lipid profiles in a young and healthy Chinese Han population. Fifty-six healthy subjects (22.89±1.80 years) were given washout diets of 31% fat and 54% carbohydrate for 7 days, followed by HC/LF diets of 15% fat and 70% carbohydrate for 6 days, with no total energy restriction. Serum lipid profiles at baseline, after washout and following HC/LF diets, as well as CETP and LDLR polymorphisms were analyzed. Carriers of B2 allele of CETP TaqIB polymorphism had significantly higher levels of high density lipoprotein cholesterol (HDL-C) and apo A-I in the whole study population after the diet intervention. Notably, males with CETP TaqIB B1B1 experienced significantly increased HDL-C and apo A-I after HC/LF diet. Regarding the LDLR Pvu II polymorphism, both P1P1 subjects and P2 carriers experienced decreased total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels after HC/LF diet with no statistically significant differences between the genotypes. Our results demonstrate that the elevated HDL-C levels after HC/LF diet in healthy Chinese Han youth are associated with CETP TaqI B2 allele while males with B1B1 genotype are more susceptible to the influence of HC/LF diet on their HDL-C levels. The decreased TC and LDL-C levels after HC/LF diet are not associated with LDLR Pvu II polymorphism.     

The association between estrogen receptor alpha polymorphisms and the risk of prostate cancer in Slovak population

The aim of our study was to evaluate the effect of two polymorphisms in the estrogen receptor alpha, PvuII and XbaI, on the development of prostate cancer within Slovak population, as well as their correlation with selected clinical characteristics. The study was performed using 311 prostate cancer patients and 256 healthy male controls. Both polymorphisms were significantly associated with higher risk of prostate cancer development. At the same time, the CC genotype of PvuII polymorphism (OR = 1.98; 95 % CI 0.94–4.21; p = 0.05) and the AG genotype of XbaI polymorphism (OR = 1.74; 95 % CI 1.0–3.02; p = 0.04) significantly contributed to the development of low-grade carcinoma, while the AG and GG genotypes of the XbaI polymorphism contributed mainly to the development of high-grade prostate cancer (OR = 1.83; 95 % CI 1.12–3.01; p = 0.01 and OR = 2.13; 95 % CI 1.06–4.19; p = 0.03, respectively). Similarly, the AG and GG genotypes of XbaI polymorphism showed significant association with prostate cancer in patients with serum PSA level ≥10 ng/ml. Both polymorphisms were found at the same time to be more frequent in patients diagnosed before the age of 60. We conclude on the basis of these results that PvuII and XbaI polymorphisms of estrogen receptor alpha might be associated with prostate cancer risk within Slovak population. Although this is a pilot study and, as such, more detailed investigations are needed to confirm the role of these polymorphisms in prostate cancer development and progression within said Slovak population, our results might still provide a valuable basis for further research with larger patient groups.     

Lifestyle factors modify obesity risk linked to PPARG2 and FTO variants in an elderly population: a cross-sectional analysis in the SUN Project

Genetic factors may interact with lifestyle factors to modify obesity risk. FTO and PPARG2 are relevant obesogenes. Our aim was to explore the effect of Pro12Ala (rs1801282) of PPARG2 and rs9939609 of FTO on obesity risk and to examine their interaction with lifestyle factors in an elderly population. Subjects (n = 978; aged 69 ± 6) were recruited from the SUN (Seguimiento Universidad de Navarra) Project. DNA was obtained from saliva, and lifestyle and dietary data were collected by validated self-reported questionnaires. Genotyping was assessed by RT-PCR plus allele discrimination. Subjects carrying the Ala allele of PPARG2 gene had a significantly increased obesity risk compared to non-carrier (Pro12Pro) subjects (OR, 1.66; 95  % CI, 1.01–2.74; p = 0.045). Greater obesity risk was also found in inactive or high carbohydrate intake subjects with the Ala12 allele of PPARG2 gene. Interestingly, subjects carrying the Ala allele of the PPARG2 gene and with a high CHO (>246 g/day) intake had an increased obesity risk compared to Pro12Pro subjects (OR, 2.67; 95 % CI, 1.3–5.46; p = 0.007; p for [CHO × PPARG2] interaction = 0.046). Moreover, in subjects with a high CHO intake, the co-presence of the Ala allele of PPARG2 gene and one minor A allele (rs9939609) of FTO gene did increase obesity risk (OR, 3.26; 95 % CI, 1.19–8.89; p = 0.021) when compared to non-carrier (Pro12Pro/TT) subjects. In conclusion, it appears that lifestyle factors may act as effect modifiers for obesity risk linked to Ala12 allele of the PPARG2 gene and the minor A allele of FTO gene in an elderly population.     

The maternal folate hydrolase gene polymorphism is associated with neural tube defects in a high-risk Chinese population

Folate hydrolase 1 (FOLH1) gene encodes intestinal folate hydrolase, which regulates intestinal absorption of dietary folate. Previous studies on the association between polymorphisms rs202676 and rs61886492 and the risk of neural tube defects (NTDs) were inconclusive. A case–control study of women with NTD-affected pregnancies (n = 160) and controls (n = 320) was conducted in the Chinese population of Lvliang, a high-risk area for NTDs. We genotyped the polymorphic sites rs202676 and rs61886492 and assessed maternal plasma folate and total homocysteine (tHcy). Our results showed that in case group, plasma folate concentrations were 18 % lower compared with those of control group (8.32 vs. 6.79 nmol/L, p = 0.033) and tHcy concentrations were 17 % higher (10.47 vs. 12.65 μmol/L, p = 0.047). Almost all samples had the rs61886492 GG genotype (99.78 %). The result showed that the frequency of GG genotype in rs202676 was significantly higher in group with multiple NTDs than in controls (p = 0.030, OR = 2.157, 95 % CI, 1.06–4.38). The multiple-NTD group showed higher maternal plasma concentrations of tHcy (10.47 vs. 13.96 μmol/L, p = 0.024). The GG genotype of rs202676 had a lower maternal folate and higher tHcy concentrations than other genotypes with no significant differences. The result of structural prediction indicated that this variation might change the spatial structure of the protein. These results suggested that the maternal polymorphism rs202676 was a potential risk factor for multiple NTDs in this Chinese population. The allele G might affect maternal plasma folate and tHcy concentration.     

Screening of lipid high producing mutant from rhodotorula glutinis by low ion implantation and study on optimization of fermentation medium

In order to obtain lipid producing strain with high-yield, the wild type stain Rhodotorula glutinis was treated by low ion implantation, and optimization of fermentation medium for higher lipid yield was carried out using mutant strain. It was found that the strain had a higher positive mutation rate when the output power was 10 keV and the dose of N⁺ implantation was 80 × 2.6 × 10¹³ ions/cm². Then a high-yield mutant strain D30 was obtained through cid-heating coupling ultrasonic method and lipid yield was 3.10 g/L. Additionally, the surface response method was used to optimize fermentation medium. The three significant factors (glucose, peptone, KH₂PO₄) were optimized using response surface methodology (RSM), and the optimized parameters of fermentation medium were as follows: glucose 73.40 g/L, peptone 1.06 g/L and KH₂PO₄ 3.56 g/L. Finally the fermentation characteristic of high-yield mutation strain D30 was studied, when fermentation time was 10 days, which lipid yield increased to 7.81 g/L. Fatty acid composition of the lipid was determined by GC, and the most represented fatty acids of mutant D30 were C16:0 (11.4 %), C16:1 (5.66 %), C18:1 (49.3 %), and C18:2 (27.0 %).     

Gualou Xiebai Banxia decoction ameliorates Poloxamer 407-induced hyperlipidemia

Ethnopharmacological relevance: Gualou Xiebai Banxia (GLXBBX) decoction is a well-known traditional Chinese herbal formula that was first discussed in the Synopsis of the Golden Chamber by Zhang Zhongjing in the Eastern Han Dynasty. In traditional Chinese medicine, GLXBBX is commonly prescribed to treat cardiovascular diseases, such as coronary heart disease and atherosclerosis.Objective: The present study aimed to examine GLXBBX’s preventative capacity and elucidate the potential molecular mechanism of Poloxamer 407 (P407)-induced hyperlipidemia in rats.Materials and methods: Both the control and model groups received pure water, and the test group also received a GLXBBX decoction. For each administration, 3 ml of the solution was administered orally. To establish hyperlipidemia, a solution mixed with 0.25 g/kg P407 dissolved in 0.9% normal saline was injected slowly into the abdominal cavity. At the end of the study, the rats’ plasma lipid levels were calculated using an automatic biochemical analyzer to evaluate the preventative capability of the GLXBBX decoction, and the serum and liver of the rats were collected.Results: The GLXBBX decoction significantly improved P407-induced hyperlipidemia, including increased plasma triglycerides (TGs), aspartate aminotransferase (AST) elevation, and lipid accumulation. Moreover, GLXBBX decoction treatment increased lipoprotein lipase (LPL) activity and mRNA expression of LPL. Furthermore, GLXBBX significantly suppressed the mRNA expression of stearoyl-CoA desaturase (SCD1).Conclusion: GLXBBX significantly improved P407-induced hyperlipidemia, which may have been related to enhanced LPL activity, increased LPL mRNA expression, and decreased mRNA expression of SCD1.     

Purification,cellular levels,and functional domains of lipase maturation factor 1

Over a third of the US adult population has hypertriglyceridemia, resulting in an increased risk of atherosclerosis, pancreatitis, and metabolic syndrome. Lipoprotein lipase (LPL), a dimeric enzyme, is the main lipase responsible for TG clearance from the blood after food intake. LPL requires an endoplasmic reticulum (ER)-resident, transmembrane protein known as lipase maturation factor 1 (LMF1) for secretion and enzymatic activity. LMF1 is believed to act as a client specific chaperone for dimeric lipases, but the precise mechanism by which LMF1 functions is not understood. Here, we examine which domains of LMF1 contribute to dimeric lipase maturation by assessing the function of truncation variants. N-terminal truncations of LMF1 show that all the domains are necessary for LPL maturation. Fluorescence microscopy and protease protection assays confirmed that these variants were properly oriented in the ER. We measured cellular levels of LMF1 and found that it is expressed at low levels and each molecule of LMF1 promotes the maturation of 50 or more molecules of LPL. Thus we provide evidence for the critical role of the N-terminus of LMF1 for the maturation of LPL and relevant ratio of chaperone to substrate.     

Two novel SNPs in the coding region of the bovine PRDM16 gene and its associations with growth traits

As a zinc-finger protein, PR domain containing 16 (PRDM16) controls brown fat determination by stimulating brown fat-selective genes expression while suppressing the expression of genes selective for white fat cells, whose mutations were associated with myelodysplastic syndrome (MDS) and leukemogenesis in human and murine model of leukemia. To date, no polymorphisms of PRDM16 gene in bovine had been reported. Herein, PCR-SSCP and DNA sequencing methods were employed to screen the genetic variation within PRDM16 gene in 1031 Chinese indigenous bovine. The results revealed two novel silent mutations: XM_001788152: m.1641T>C (547aa), 1881G>A (627aa). Hence, we described the PvuII and HaeIII forced PCR–RFLP methods for detecting these mutations, respectively. In the forced PCR–RFLP analysis with PvuII, the frequencies of bovine PRDM16-C allele varied from 0.044 to 0.506 in four Chinese native breeds. In the forced PCR–RFLP analysis with HaeIII, the frequencies of bovine PRDM16-G allele were 0.474, 0.494, 0.576 and 0.906 for Jiaxian (JX), Nanyang (NY), Qinchuan (QC) and Chinese Holstein (CH) population. Significant statistical differences between genotypic frequencies implied that both of the polymorphic loci were significantly associated with cattle breeds by the chi square test (χ² = 190.058, P < 0.001 and χ² = 118.239, P < 0.001 for PvuII; χ² = 209.842, P < 0.001 and χ² = 108.711, P < 0.001 for HaeIII). The associations of the PvuII and HaeIII forced PCR–RFLPs of bovine PRDM16 loci with growth traits were analyzed in Nanyang breed. The two SNPs were associated with body weight and average daily gain in Nanyang aged 12 months, individuals with genotype TT and AA showed significantly better body weight (P < 0.05) and average daily gain (P < 0.01) at 12 months, respectively.     

Probiotic Bacillus amyloliquefaciens SC06 Prevents Bacterial Translocation in Weaned Mice

Probiotic is a preparation containing microorganisms that confers beneficial effect to the host. This work assessed whether oral administration of Bacillus amyloliquefaciens SC06 (Ba) could decrease bacterial translocation in weaned mice. Weaned C57BL/6 were randomly allocated into three groups: group I as the control group, group II were treated with 0.85 % NaCl. Group III was administered with probiotic Ba 1 × 10⁹ CFU/day dissolved in 100 μl of 0.85 % NaCl for 30 days. Mice were then sacrificed, and tissue were cultured to determine bacterial translocation. Meanwhile, splenic CD4⁺T cells, CD8⁺T cells, B cells, and macrophages were analysised by FACS. Our results showed that probiotic Ba significantly reduced bacteria translocation compared with the control group and 0.85 % NaCl group (P < 0.05), lower levels of bacteria were detected in the MLN, liver, spleen, and kidney of mice. Moreover, significant increase in percentage and number of macrophages were observed in the spleen of Ba-treated mice compared with the control and 0.85 % NaCl groups. Together, these data indicated that Ba could decrease bacterial translocation in weaned mice. This effect seems to be correlated with the changes of macrophage numbers.     

Effects of Clostridium butyricum and Enterococcus faecium on growth performance, lipid metabolism, and cecal microbiota of broiler chickens

To investigate the effects of Clostridium butyricum and Enterococcus faecium on the growth performance, lipid metabolism, and cecal microbiota of broilers, 264 one-day-old male Ross 308 broiler chicks were randomly allocated into four treatments with six replicates in a 2?×?2 factorial arrangement and fed four diets with two levels of C. butyricum (0 or 1?×?10⁹ cfu/kg) and two levels of E. faecium (0 or 2?×?10⁹ cfu/kg) for 42 days. There was no significant interaction between C. butyricum and E. faecium on the growth performance, lipid metabolism, and cecal microbiota of broilers. However, broilers supplemented with E. faecium had lower (P?=?0.022) serum leptin level at day 21 and higher (P?<?0.001) fatty acid synthase (FAS), malic enzyme (ME), and acetyl–CoA carboxylase (ACC) mRNA levels in the liver at day 42. Supplementation of C. butyricum improved (P?<?0.05) the average daily feed intake and average daily gain, increased (P?=?0.016) the serum insulin level at 21 days of age, enhanced (P?<?0.05) the content of intramuscular fat, activities of FAS in the liver and lipoprotein lipase (LPL) in the breast muscle, mRNA expression of FAS, ME, and ACC in the liver and LPL in the breast muscle at 42 days of age, but reduced (P?=?0.030) cecal Bacteroidetes relative abundance at 21 days of age. The results of this study indicate that the increased intramuscular fat content of broilers fed C. butyricum as observed may be the result of enhanced lipogenesis.     

ISSR and DAMD markers revealed high genetic variability within Flavoparmelia caperata in Western Himalaya (India)

Flavoparmelia caperata (L.) Hale is medicinally very important and possesses antifungal and antibacterial activities. F. caperata is the only species found in India. Inter simple sequence repeat (ISSR) and Directed amplification of minisatellite DNA (DAMD) methods were used to analyze the genetic variability within F. caperata from the Western Himalayan region of India. Eleven ISSR and 10 DAMD primers produced 139 and 117 polymorphic bands, and detected 91.44 and 82.34 % polymorphisms, respectively. Cumulative band data generated for ISSR and DAMD markers resulted in 86.86 % polymorphism across all the accessions of F. caperata. The average Polymorphic information content (PIC) value obtained with ISSR, DAMD, and cumulative band data were 0.28, 0.27, and 0.27, respectively. The clustering of the F. caperata accessions in the UPGMA dendrogram showed that these accessions are intermingled with each other in different subclusters irrespective of their geographical affiliations. The pattern of genetic variations within F. caperata accessions could be due to free exchange of spores that might have taken place among these accessions in the wild. ISSR and DAMD markers efficiently and reliably resulted in discrete banding patterns and polymorphic profiles. These markers despite targeting different regions of genome, revealed almost similar levels of polymorphism across all the accessions. The wide range of genetic distance and high level of polymorphism detected by ISSR and DAMD reflected a high genetic variability among the different accessions of F. caperata.     

Ecobiotechnological Approach for Exploiting the Abilities of Bacillus to Produce Co-polymer of Polyhydroxyalkanoate

Ecobiotechnological approach is an attractive and economical strategy to enrich beneficial microbes on waste biomass for production of Polyhydroxyalkanoate (PHA). Here, six strains of Bacillus spp. were used to produce co-polymers of PHA from pea-shells. Of the 57 mixed bacterial cultures (BCs) screened, two of the BCs, designated as 5BC1 and 5BC2, each containing 5 strains could produce PHA co-polymer at the rate of 505–560 mg/l from feed consisting of pea-shell slurry (PSS, 2 % total solids) and 1 % glucose (w/v). Co-polymer production was enhanced from 65–560 mg/l on untreated PSS to 1,610–1,645 mg/l from PSS treated with defined hydrolytic bacteria and 1 % glucose. Supplementation of the PSS hydrolysate with sodium propionate enabled 5BC1 to produce co-polymer P(3HB-co-3HV) with a 3HV content up to 13 % and a concomitant 1.46-fold enhancement in PHA yield. Using the principles of ecobiotechnology, this is the first demonstration of PHA co-polymer production by defined co-cultures of Bacillus from biowaste as feed under non-axenic conditions.     

The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats

Little is known about the effective role of Hypericum perforatum on hepatic ischemia–reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE₅₀) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE₅₀ significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment–control group (p < 0.05). In oxidative stress generated by hepatic ischemia–reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body.     

Ginseng Panaxoside Rb1 Reduces Body Weight in Diet-Induced Obese Mice

Crude extracts from ginseng demonstrated anti-obesity properties. Ginsenoside Rb1 is the main component of ginseng, however, there are only few studies examining its effects in obesity. In the present study, we evaluated its potential anti-obesity effects in the murine model of diet-induced obesity. Seventy male C57BL/6 mice were randomly divided to consume for 12 weeks either chow diet (N = 8) or high-fat (HF) diet (N = 62). The latter mice were then divided into four groups: diet-induced obesity group (DIO; N = 10), obesity-resistant group (OR; N = 10), HF group (N = 5), and the group whose diet was changed from HF to normal diet (DC; N = 5). Intraperitoneal injections of Rb-1 were administered daily to mice in the DIO and OR groups for 3 weeks. Body weight and energy intake were monitored, and fasting blood glucose, lipids, neuropeptide Y, Y2 receptor, and peptide YY were quantified. Compared with HF group, weight gain and food intake of DIO mice with Rb-1 injection was significantly decreased (p < 0.05). Further, levels of blood glucose and some lipids were also decreased in DIO-Rb1 group compared with HF group. Furthermore, Rb1 was also found to modulate serum levels of PYY and NPY, and mRNA expression of NPY, Y2 receptor and PYY in tissue samples of DIO mice. Taken together, ginsenoside Rb1 may be useful in the treatment of obesity via modifying the serum content and mRNA expression of NPY, Y2 receptor and PYY.     

Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma

OBJECTIVES:

Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma.

MATERIALS AND METHODS:

In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes.

RESULTS:

Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0.093) frequencies. But the C/C genotype of the PvuII site and G/G genotype of the XbaI site in the ESR1 gene were associated significantly with the risk of developing prostate carcinoma. The G/G, G/A and A/A genotypes of the COMT gene were observed in 50%, 29% and 21% of control patients and in 53%, 21% and 26% of case patients, respectively. The A and G allele frequencies of the COMT gene were observed in 36.7%, 63.3% of control patients and in 36.8%, 63.2% of case patients, respectively. In COMT gene, there was not any significant difference in terms of genotype (P = 0.843) and allele (P = 0.991) frequencies. But the G/A genotype of the COMT gene had a weak tendency toward increased risk.

CONCLUSION:

Polymorphisms of ESR1 gene in the estrogen metabolism pathway were associated significantly with familial prostate carcinoma risk. Single nucleotide polymorphisms of low-penetrance genes are targets for understanding the genetic susceptibility of familial prostate carcinoma.     

Influence of Matrix Metalloproteinase-1 Gene −1607 (1G/2G) (rs1799750) Promoter Polymorphism on Circulating Levels of MMP-1 in Chronic Pancreatitis

This study investigated the role of ?1607 (1G/2G) (rs1799750) polymorphism of the MMP-1 gene in chronic pancreatitis. We genotyped 100 patients with chronic pancreatitis and 100 control subjects using tetra-primer ARMS-PCR followed by agarose gel electrophoresis. Serum levels of MMP-1 were determined by Elisa. Statistical analysis was applied to test the significance of the results. The genotypic and allelic distribution varied significantly between the disease group and the control subjects [OD = 1.981 (1.236–3.181), p = 0.004]. MMP-1 levels were higher in subjects homozygous for the 2G allele than in subjects with the 1G allele. The present study revealed a significant association of the MMP-1 ?1607 1G/2G (rs1799750) gene promoter polymorphism with chronic pancreatitis, and it can be considered a biological marker in the etiology of chronic pancreatitis.     

The Leu72Met polymorphism of the GHRL gene prevents the development of diabetic nephropathy in Chinese patients with type 2 diabetes mellitus

The preproghrelin (GHRL) Leu72Met polymorphism (rs 696217) is associated with obesity, reduced glucose-induced insulin secretion in healthy or diabetic subjects, and reduced serum creatinine (Scr) levels in type 2 diabetes. We evaluated the association of the Leu72Met polymorphism with measures of insulin sensitivity in non-diabetic control individuals and type 2 diabetics, and whether this variation contributes to the development of diabetic nephropathy (DN) in type 2 diabetes. A case–control study was performed of 291 non-diabetic control subjects and 466 patients with type 2 diabetes, of whom 238 had DN with overt albuminuria (DN group; albuminuric excretion rate [AER] ≥ 300 mg/24 h) and 228 did not have DN, but had diabetes for more than 10 years (non-DN group). Genotyping was performed using a TaqMan PCR assay. The Leu/Leu, Leu/Met, and Met/Met genotype frequencies were significantly different between the non-DN and DN groups (p = 0.011). The frequency of the variant genotypes (Leu/Met, Met/Met) was significantly lower in the DN group than the non-DN group (23.5 vs. 36.0 %, p = 0.003). Met/Met non-diabetic control subjects had lower BMI and Scr levels and higher eGFR level than Leu/Leu or Leu/Met individuals (p < 0.05). Leu/Met and Met/Met type 2 diabetics had significantly lower AER and Scr levels and higher eGFR level than Leu/Leu type 2 diabetics (all p < 0.001). The GHRL Leu72Met polymorphism may help to maintain normal renal function and may protect against the development of DN by reducing albuminuria and improving renal function in Chinese patients with type 2 diabetes.     

A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer

Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04–1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14–1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85–0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.