Metabolic profiling of smoking, associations with type 2 diabetes and interaction with genetic susceptibility.

BACKGROUND: Smokers are at increased risk of type 2 diabetes (T2D), but the underlying mechanisms are unclear. We investigated if the smoking-T2D association is mediated by alterations in the metabolome and assessed potential interaction with genetic susceptibility to diabetes or insulin resistance. METHODS: In UK Biobank (n = 93,722), cross-sectional analyses identified 208 metabolites associated with smoking, of which 131 were confirmed in Mendelian Randomization analyses, including glycoprotein acetyls, fatty acids, and lipids. Elastic net regression was applied to create a smoking-related metabolic signature. We estimated hazard ratios (HR) of incident T2D in relation to baseline smoking/metabolic signature and calculated the proportion of the smoking-T2D association mediated by the signature. Additive interaction between the signature and genetic risk scores for T2D (GRS-T2D) and insulin resistance (GRS-IR) on incidence of T2D was assessed as relative excess risk due to interaction (RERI). FINDINGS: The HR of T2D was 1·73 (95% confidence interval (CI) 1·54 - 1·94) for current versus never smoking, and 38·3% of the excess risk was mediated by the metabolic signature. The metabolic signature and its mediation role were replicated in TwinGene. The metabolic signature was associated with T2D (HR: 1·61, CI 1·46 - 1·77 for values above vs. below median), with evidence of interaction with GRS-T2D (RERI: 0·81, CI: 0·23 - 1·38) and GRS-IR (RERI 0·47, CI: 0·02 - 0·92). INTERPRETATION: The increased risk of T2D in smokers may be mediated through effects on the metabolome, and the influence of such metabolic alterations on diabetes risk may be amplified in individuals with genetic susceptibility to T2D or insulin resistance.

Childhood adiposity and novel subtypes of adult-onset diabetes: a Mendelian randomisation and genome-wide genetic correlation study.

AIMS/HYPOTHESIS: We investigated whether the impacts of childhood adiposity on adult-onset diabetes differ across proposed diabetes subtypes using a Mendelian randomisation (MR) design. METHODS: We performed MR analysis using data from European genome-wide association studies of childhood adiposity, latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). RESULTS: Higher levels of childhood adiposity had positive genetically predicted effects on LADA (OR 1.62, 95% CI 1.05, 2.52), SIDD (OR 2.11, 95% CI 1.18, 3.80), SIRD (OR 2.76, 95% CI 1.60, 4.75) and MOD (OR 7.30, 95% CI 4.17, 12.78), but not MARD (OR 1.06, 95% CI 0.70, 1.60). CONCLUSIONS/INTERPRETATION: Childhood adiposity is a risk factor not only for adult-onset diabetes primarily characterised by obesity or insulin resistance, but also for subtypes primarily characterised by insulin deficiency or autoimmunity. These findings emphasise the importance of preventing childhood obesity.

Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults.

AIMS/HYPOTHESES: Smoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes. METHODS: Analyses were based on Swedish case-control data (collected 2010-2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984-2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case-control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was conducted based on summary statistics from genome-wide association studies. RESULTS: Smoking (RRpooled 1.30 [95% CI 1.06, 1.59] for current vs never) and snus use (OR 1.97 [95% CI 1.20, 3.24] for ≥15 box-years vs never use) were associated with an increased risk of LADA. Corresponding estimates for type 2 diabetes were 1.38 (95% CI 1.28, 1.49) and 1.92 (95% CI 1.27, 2.90), respectively. There was interaction between smoking and HLA high-risk genotypes (AP 0.27 [95% CI 0.01, 0.53]) in relation to LADA. The positive association between smoking and LADA/type 2 diabetes was confirmed by the MR study. CONCLUSIONS/INTERPRETATION: Our findings suggest that tobacco use increases the risk of LADA and that smoking acts synergistically with genetic susceptibility in the promotion of LADA. DATA AVAILABILITY: Analysis codes are shared through GitHub ( https://github.com/jeseds/Smoking-use-of-smokeless-tobacco-HLA-genotypes-and-incidence-of-LADA ).

[Study of the association of lncRNA-GAS5 gene polymorphisms with systemic lupus erythematosus in Guangxi population].

OBJECTIVE: To assess the association of rs55829688 and rs75315904 polymorphisms of the lncRNA-GAS5 gene with susceptibility to systemic lupus erythematosus (SLE) in Guangxi population. METHODS: Peripheral venous blood samples were collected from the SLE group and control group. Following extraction of genomic DNA, SNPscan and Sanger sequencing were carried out to determine the genotypes for the rs55829688 and rs75315904 loci of the lncRNA-GAS5 gene. RESULTS: No difference was found between the two groups with regard to the genotypic frequencies for rs55829688 and rs75315904 (P > 0.05). However, the frequencies of C allele of rs55829688 between the two groups was significantly different (P < 0.05). In the SLE group, the frequencies of C allele and CT+CC genotype for rs55829688 among SLE patients with nephritis were significantly lower than those of SLE patients without nephritis (P < 0.05). In addition, haplotype analysis showed that the frequency of rs55829688 C/rs75315904 A allele in the SLE group was lower than that of the control group (P < 0.05). CONCLUSION: In Guangxi population, the carrier status of rs55829688 C allele of the lncRNA-GAS5 gene may reduce the risk of SLE and its complicated nephritis, and the rs55829688 C/rs75315904 A haplotype may reduce the risk for SLE.

Birthweight, BMI in adulthood and latent autoimmune diabetes in adults: a Mendelian randomisation study.

AIMS/HYPOTHESIS: Observational studies have found an increased risk of latent autoimmune diabetes in adults (LADA) associated with low birthweight and adult overweight/obese status. We aimed to investigate whether these associations are causal, using a two-sample Mendelian randomisation (MR) design. In addition, we compared results for LADA and type 2 diabetes. METHODS: We identified 43 SNPs acting through the fetal genome as instrumental variables (IVs) for own birthweight from a genome-wide association study (GWAS) of the Early Growth Genetics Consortium (EGG) and the UK Biobank. We identified 820 SNPs as IVs for adult BMI from a GWAS of the UK Biobank and the Genetic Investigation of ANthropometric Traits consortium (GIANT). Summary statistics for the associations between IVs and LADA were extracted from the only GWAS involving 2634 cases and 5947 population controls. We used the inverse-variance weighted (IVW) estimator as our primary analysis, supplemented by a series of sensitivity analyses. RESULTS: Genetically determined own birthweight was inversely associated with LADA (OR per SD [~500 g] decrease in birthweight 1.68 [95% CI 1.01, 2.82]). In contrast, genetically predicted BMI in adulthood was positively associated with LADA (OR per SD [~4.8 kg/m2] increase in BMI 1.40 [95% CI 1.14, 1.71]). Robust results were obtained in a range of sensitivity analyses using other MR estimators or excluding some IVs. With respect to type 2 diabetes, the association with birthweight was not stronger than in LADA while the association with adult BMI was stronger than in LADA. CONCLUSIONS/ INTERPRETATION: This study provides genetic support for a causal link between low birthweight, adult overweight/obese status and LADA.

Maternal smoking during pregnancy and type 1 diabetes in the offspring: a nationwide register-based study with family-based designs.

BACKGROUND: Maternal smoking during pregnancy was reported to be associated with a reduced risk of type 1 diabetes in the offspring. We investigated whether this association is consistent with a causal interpretation by accounting for familial (shared genetic and environmental) factors using family-based, quasi-experimental designs. METHODS: We included 2,995,321 children born in Sweden between 1983 and 2014 and followed them for a diagnosis of type 1 diabetes until 2020 through the National Patient, Diabetes and Prescribed Drug Registers. Apart from conducting a traditional cohort study, we performed a nested case-control study (quasi-experiment) comparing children with type 1 diabetes to their age-matched siblings (or cousins). Information on maternal smoking during pregnancy was retrieved from the Swedish Medical Birth Register. Multivariable adjusted Cox proportional hazards regression and conditional logistic regression were used. RESULTS: A total of 18,617 children developed type 1 diabetes, with a median age at diagnosis of 9.4 years. The sibling and cousin comparison design included 14,284 and 7988 of these children, respectively. Maternal smoking during pregnancy was associated with a 22% lower risk of offspring type 1 diabetes in the full cohort (hazard ratio 0.78, 95% confidence interval [CI] 0.75-0.82). The corresponding odds ratio was 0.78 (95% CI 0.69-0.88) in the sibling and 0.72 (95% CI 0.66-0.79) in the cousin comparison analysis. CONCLUSIONS: This nationwide, family-based study provides support for a protective effect of maternal smoking on offspring type 1 diabetes. Mechanistic studies are needed to elucidate the underlying pathways behind this link.

Efficient D-allulose synthesis under acidic conditions by auto-inducing expression of the tandem D-allulose 3-epimerase genes in Bacillus subtilis.

BACKGROUND: D-allulose, a hexulose monosaccharide with low calorie content and high sweetness, is commonly used as a functional sugar in food and nutrition. However, enzyme preparation of D-allulose from D-frutose was severely hindered by the non-enzymatic browning under alkaline and high-temperature, and the unnecessary by-products further increased the difficulties in separation and extraction for industrial applications. Here, to address the above issue during the production process, a tandem D-allulose 3-epimerase (DPEases) isomerase synergistic expression strategy and an auto-inducible promoter engineering were levered in Bacillus subtilis 168 (Bs168) for efficient synthesis of D-allulose under the acidic conditions without browning. RESULTS: First, based on the dicistron expression system, two DPEases with complementary functional characteristics from Dorea sp. CAG:317 (DSdpe) and Clostridium cellulolyticum H10 (RCdpe) were expressed in tandem under the promoter HpaII in one cell. A better potential strain Bs168/pMA5-DSdpe-RCdpe increases enzyme activity to 18.9 U/mL at acidic conditions (pH 6.5), much higher than 17.2 and 16.7 U/mL of Bs168/pMA5-DSdpe and Bs168/pMA5-RCdpe, respectively. Subsequently, six recombinant strains based on four constitutive promoters were constructed in variable expression cassettes for improving the expression level of protein. Among those engineered strains, Bs168/pMA5-PspoVG-DSdpe-PsrfA-RCdpe exhibited the highest enzyme activity with 480.1 U/mL on fed-batch fermentation process in a 5 L fermenter at pH 6.5, about 2.1-times higher than the 228.5 U/mL of flask fermentation. Finally, the maximum yield of D-allulose reached as high as 163.5 g/L at the fructose concentration (50% w/v) by whole-cell biocatalyst. CONCLUSION: In this work, the engineered recombinant strain Bs168/pMA5-PspoVG-DSdpe-PsrfA-RCdpe was demonstrated as an effective microbial cell factory for the high-efficient synthesis of D-allulose without browning under acidic conditions. Based on the perspectives from this research, this strategy presented here also made it possible to meet the requirements of the industrial hyper-production of other rare sugars under more acidic conditions in theory.

LncRNA HOTAIR regulates the expression of E-cadherin to affect nasopharyngeal carcinoma progression by recruiting histone methylase EZH2 to mediate H3K27 trimethylation.

BACKGROUND/AIM: There has been increasing evidence for the function of long non-coding RNA (lncRNA) in nasopharyngeal carcinoma (NPC). We aim to delve into the position of lncRNA HOX antisense intergenic RNA (HOTAIR), together with enhancer of zeste homolog 2 (EZH2), E-cadherin and trimethylation of lysine 27 on histone H3 (H3K27me3) in NPC. METHODS: HOTAIR, EZH2, and E-cadherin expression in NPC tissues and cells were tested. NPC cell biological functions were examined through gain-of and loss-of function assays. The mechanism of lncRNA HOTAIR/E-cadherin/EZH2/H3K27 axis in NPC was decoded. RESULTS: LncRNA HOTAIR and EZH2 were highly expressed in NPC, and E-cadherin was lowly expressed. Down-regulation of HOTAIR or EZH2 inhibited NPC cell progression and tumor growth. HOTAIR recruited histone methylase EZH2 to mediate trimethylation of H3K27 and regulated E-cadherin expression. CONCLUSION: HOTAIR inhibits E-cadherin by stimulating the trimethylation of H3K27 to promote NPC cell progression through recruiting histone methylase EZH2.

Research Progress on Small Molecular Inhibitors of the Type 3 Secretion System.

The overuse of antibiotics has led to severe bacterial drug resistance. Blocking pathogen virulence devices is a highly effective approach to combating bacterial resistance worldwide. Type three secretion systems (T3SSs) are significant virulence factors in Gram-negative pathogens. Inhibition of these systems can effectively weaken infection whilst having no significant effect on bacterial growth. Therefore, T3SS inhibitors may be a powerful weapon against resistance in Gram-negative bacteria, and there has been increasing interest in the research and development of T3SS inhibitors. This review outlines several reported small-molecule inhibitors of the T3SS, covering those of synthetic and natural origin, including their sources, structures, and mechanisms of action.

Characteristics of spicy food consumption and its relation to lifestyle behaviours: results from 0.5 million adults.

This study aimed to describe the characteristics and lifestyle differences of spicy food consumption in 0.5 million adults. Participants were recruited from 2004 to 2008 in the baseline research of the CKB study. Higher frequency and stronger pungency degree in spicy food positively correlated with preference for salty taste, eating snacks/deep-fried foods, tea/alcohol drinking and tobacco smoking. Among weekly tea/alcohol drinkers and current regular smokers, participants with a higher frequency of spicy food consumption or preference for stronger pungency degree were more likely to prefer strong tea, drink alcohol exceed the healthy amount, drink alcohol in the morning every day, smoke ≥ 40 cigarettes per day, consume a larger amount of tea leaves, alcohol and cigarettes each day, and start habitual tea/alcohol drinking or smoking at an earlier age. Differences existed in lifestyle factors related to major chronic diseases according to spicy food consumption frequency and pungency degree among the Chinese population.

[Correlation of single nucleotide polymorphisms of the osteopontin gene with astheozoospermia].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms (SNP) rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 of the osteopontin (OPN) gene with the risk of asthenozoospermia (AZS). METHODS: We included 135 AZS patients in the AZS group and another 239 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 polymorphisms of the OPN gene in all the subjects and analyzed the correlation of the five SNPs with AZS. RESULTS: The GA genotype and A allele of the OPN gene rs1126772 were found to be correlated with the risk of AZS (GA vs AA: OR = 0.55, 95% CI: 0.35－0.86, P = 0.009; A vs G: OR = 0.64, 95% CI: 0.46－0.89, P = 0.007), and so was the CT genotype and T allele at the RS11730582 locus (CT vs TT: OR = 0.526, 95% CI: 0.34－0.82, P = 0.009; T vs C: OR = 0.60, 95% CI: 0.44－0.83, P = 0.002). Haplotype analysis showed that the AATCT haplotype decreased the risk of AZS (AATCT: OR = 0.61, 95% CI: 0.42－0.88, P = 0.008) . CONCLUSIONS: The polymorphisms of the OPN gene RS1126772 and RS11730582 may reduce the risk of AZS.

Association between adiposity measures and COPD risk in Chinese adults.

Bodyweight and fat distribution may be related to COPD risk. Limited prospective evidence linked COPD to abdominal adiposity. We investigated the association of body mass index (BMI) and measures of abdominal adiposity with COPD risk in a prospective cohort study.The China Kadoorie Biobank recruited participants aged 30-79 years from 10 areas across China. Anthropometric indexes were objectively measured at the baseline survey during 2004-2008. After exclusion of participants with prevalent COPD and major chronic diseases, 452 259 participants were included and followed-up until the end of 2016. We used Cox models to estimate adjusted hazard ratios relating adiposity to risk of COPD hospitalisation or death.Over an average of 10.1 years of follow-up, 10 739 COPD hospitalisation events and deaths were reported. Compared with subjects with normal BMI (18.5-<24.0 kg·m-2), underweight (BMI <18.5 kg·m-2) individuals had increased risk of COPD, with adjusted hazard ratio 1.78 (95% CI 1.66-1.89). Overweight (BMI 24.0-<28.0 kg·m-2) and obesity (BMI ≥28.0 kg·m-2) were not associated with an increased risk after adjustment for waist circumference. A higher waist circumference (≥85 cm for males and ≥80 cm for females) was positively associated with COPD risk after adjustment for BMI. Additionally, waist-to-hip ratio and waist-to-height ratio were positively related to COPD risk.Abdominal adiposity and underweight were risk factors for COPD in Chinese adults. Both BMI and measures of abdominal adiposity should be considered in the prevention of COPD.

Body-mass index and long-term risk of sepsis-related mortality: a population-based cohort study of 0.5 million Chinese adults.

BACKGROUND: Sepsis represents a major worldwide healthcare burden. However, how body-mass index (BMI) is related to the long-term risk of sepsis-related mortality in low- and middle-income countries remains uncertain. METHODS: We examined the associations of sepsis-related mortality with both baseline BMI and waist circumference (WC) using data from China Kadoorie Biobank, a prospective cohort recruited during 2004-2008 and followed up to December 2016. After excluding participants with chronic obstructive pulmonary disease, tuberculosis, cancer, heart disease, and stroke, and omitting the first 3 years of follow-up, 440,763 participants remained for analysis. RESULTS: During a median follow-up of 10.0 years, 1957 sepsis-related deaths (3,134,870 person-years) were included for analysis. Compared with reference BMI of 22.5 to < 25.0 kg/m2, the multivariable-adjusted hazard ratios (HRs) for sepsis-related mortality were 2.42 (95% CIs 2.07-2.84) for BMI of < 18.5, 1.59 (1.36-1.85) for 18.5 to < 20.0, 1.21 (1.06-1.38) for 20.0 to < 22.5, 0.97 (0.83-1.13) for 25.0 to < 27.5, 0.98 (0.80-1.21) for 27.5 to < 30.0, and 1.22 (0.93-1.60) for ≥ 30.0 kg/m2. Further adjustment for WC led to slightly augmentation of the effect size for the lower BMI groups and null association in the obese group. In the association analysis between WC and sepsis-related mortality, compared with the middle quintile group, only the highest quintile group showed an increased risk of sepsis-related mortality after adjusted for BMI (HR = 1.54; 95% CI 1.28-1.84). CONCLUSIONS: Underweight, lower normal weight, and abdominal obesity are associated with increased future risk of sepsis-related mortality over 10 years in the Chinese population. The double burden of underweight and obesity indicates a heavy sepsis burden faced by low- and middle-income countries.

Soy intake and breast cancer risk: a prospective study of 300,000 Chinese women and a dose-response meta-analysis.

Epidemiological evidence on the association of soy intake with breast cancer risk is still inconsistent due to different soy intake levels across previous studies and small number of breast cancer cases. We aimed to investigate this issue by analyzing data from the China Kadoorie Biobank (CKB) study and conducting a dose-response meta-analysis to integrate existing evidence. The CKB study included over 300,000 women aged 30-79 from 10 regions across China enrolled between 2004 and 2008, and followed-up for breast cancer events until 31 December 2016. Information on soy intake was collected from baseline, two resurveys and twelve 24-h dietary recalls. We also searched for relevant prospective cohort studies to do a dose-response meta-analysis. The mean (SD) soy intake was 9.4 (5.4) mg/day soy isoflavones among CKB women. During 10 years of follow-up, 2289 women developed breast cancers. The multivariable-adjusted relative risk was 1.00 (95% confidence interval [CI] 0.81-1.22) for the fourth (19.1 mg/day) versus the first (4.5 mg/day) soy isoflavone intake quartile. Meta-analysis of prospective studies found that each 10 mg/day increment in soy isoflavone intake was associated with a 3% (95% CI 1-5%) reduced risk of breast cancer. The CKB study demonstrated that moderate soy intake was not associated with breast cancer risk among Chinese women. Higher amount of soy intake might provide reasonable benefits for the prevention of breast cancer.

Association of interleukin-27 gene polymorphisms with susceptibility to HIV infection and disease progression.

Interleukin-27 (IL-27) gene polymorphisms are linked to infectious disease susceptibility and IL-27 plasma level is associated with HIV infection. Therefore, we aimed to investigate the association between IL-27 polymorphisms and susceptibility to HIV infection and disease progression. A total of 300 patients with HIV infection (48 long-term nonprogressors and 252 typical progressors) and 300 healthy controls were genotyped for three IL-27 polymorphisms, rs17855750, rs181206, rs40837 which were performed by using multiple single nucleotide primer extension technique. Significant association was found between IL-27 rs40837 polymorphisms with susceptibility to HIV infection (AG vs AA: adjusted OR = 1.60, 95% CI, 1.11-2.30, P = 0.012; AG+GG vs AA: adjusted OR = 1.44, 95% CI, 1.02-2.03, P = 0.038) and disease progression (LTNP: AG vs AA: adjusted OR = 2.33, 95% CI, 1.13-4.80, P = 0.021; TP: AG vs AA: adjusted OR = 1.50, 95% CI, 1.04-2.24, P = 0.030). Serum IL-27 levels were significantly lower in cases compared to controls (P < 0.001). There were lower serum IL-27 levels in TPs than in LTNPs (P < 0.001). We further found that LTNPs with rs40837 AG or GG genotype had lower serum IL-27 levels than with AA genotype (P < 0.05). The CD4+ T counts in cases were significantly lower than controls (P < 0.001). In contrast, individuals with rs40837 AG genotype had lower CD4+ T counts than with AA genotype in cases (P < 0.05). In addition, CD4+ T counts in TPs were significantly lower than LTNPs (P < 0.001). IL-27 rs40837 polymorphism might influence the susceptibility to HIV infection and disease progression probably by regulating the level of serum IL-27 or the quantity of CD4+ T.

Exosomal lncRNA HNF1A-AS1 affects cisplatin resistance in cervical cancer cells through regulating microRNA-34b/TUFT1 axis.

BACKGROUND: There is growing evidence of the role of long non-coding RNAs (lncRNAs) in cervical cancer (CC). The objective was to discuss whether exosomal lncRNA HNF1A-AS1 impacted drug resistance in CC via binding to microRNA-34b (miR-34b) and regulating TUFT1 expression. METHODS: The expression of HNF1A-AS1 in normal cervical epithelial cells, cisplatin (DDP)-sensitive cell line (HeLa/S) and DDP-resistant cell line (HeLa/DDP) cells were detected. HeLa/S and HeLa/DDP cells were interfered with HNF1A-AS1 to determine IC50, proliferation, colony formation and apoptosis of CC cells. The exosomes were isolated and identified. Subcellular localization of HNF1A-AS1, expression of miR-34b and TUFT1 in receptor cells were also verified. The binding site between HNF1A-AS1 and miR-34b, together with miR-34b and TUFT1 were confirmed. Tumorigenic ability of cells in nude mice was also detected. RESULTS: HNF1A-AS1 was upregulated in DDP-resistant cell line HeLa/DDP. Silencing HNF1A-AS1 suppressed CC cell proliferation and promoted its apoptosis. HNF1A-AS1 was found to act as a competing endogenous RNA (ceRNA) of miR-34b to promote the expression of TUFT1. Exosomes shuttled HNF1A-AS1 promoted the proliferation and drug resistance of CC cells and inhibited their apoptosis by upregulating the expression of TUFT1 and downregulating miR-34b. Furthermore, suppressed exosomal HNF1A-AS1 in combination with DDP inhibited tumor growth in nude mice. CONCLUSION: Our study provides evidence that CC-secreted exosomes carrying HNF1A-AS1 as a ceRNA of miR-34b to promote the expression of TUFT1, thereby promoting the DDP resistance in CC cells.

Genetic association of promoter in GRP78 gene with nasopharyngeal carcinoma in a Chinese population.

BACKGROUND: Emerging evidences were accumulated to support the view that GRP78 might be associated with multiple types of cancer. Given these, the aim of this study is to investigate the relationship between single nucleotide polymorphisms (SNPs) of GRP78 gene promoter and nasopharyngeal carcinoma (NPC). METHODS: Three SNPs (rs3216733, rs17840761 and rs17840762) in GRR78 promoter were estimated in 422 NPC patients and 452 controls. Genotyping was performed using SNaPshot SNP. Serum GRP78 level was performed by enzyme-linked immunosorbent assay (ELISA). Data were analyzed by SPSS 17.0 software. RESULTS: Significant association between rs3216733 polymorphism and NPC was observed (Cd vs. dd: OR = 0.57, 95% CI 0.43-0.76, P < 0.001; CC vs. dd: OR = 0.62, 95% CI 0.39-0.98, P = 0.043; Cd/CC vs. dd: OR = 0.58, 95% CI 0.44-0.76, P < 0.001; C vs. d OR = 0.70, 95% CI 0.57-0.86, P = 0.001). Additionally, we further found that expression were down-regulated in serum of patients with NPC carrying rs3216733 CC genotype when compared to that of dd genotype (P < 0.001). CONCLUSION: The observations suggest that rs3216733 polymorphism in the GRP78 gene promoter may correlate with NPC susceptibility.

[Asthenozoospermia is not correlated with 3' UTR polymorphisms of the GRP78 gene].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms (SNPs) rs12009, rs1140763 and rs16927997 in the 3'-untranslated region (3'UTR) of the glucose-regulated protein 78 (GRP78) gene with the risk of male asthenozoospermia (AZS). METHODS: We included 400 AZS patients in the AZS group and another 400 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs12009, rs1140763 and rs16927997 polymorphisms in the 3'UTR of the GRP78 gene in all the male subjects and analyzed the association of the three SNPs with AZS. RESULTS: The percentage of progressively motile sperm was significantly lower in the AZS group than in the normal controls (ï¼»20.09 ± 8.18ï¼½ % vs ï¼»57.16 ± 13.45ï¼½ %, P <0.01). Three genotypes of CC, CT and TT and 2 alleles of C and T were found in rs12009 and rs1140763 of the GRP78 gene, and another three genotypes of GG, GA and AA and two alleles of G and A were observed in rs16927997. There were no statistically significant differences between the control and AZS groups in the frequencies of the C and T alleles in rs12009 (44.3% vs 47.3% and 55.7% vs 52.7%, P >0.05) or rs1140763 (50.0% vs 52.0% and 50.0% vs 48.0%, P >0.05) or those of the G and A alleles in rs16927997 (6.0% vs 4.4% and 94.0% vs 95.6%, P >0.05), nor in the genotypes and allele frequencies of the 3 polymorphisms (P >0.05). Furthermore, three haplotypes of C-C-A, T-C-G and T-T-A were observed in the male subjects but showed no evident correlation between the AZS and normal control groups. CONCLUSIONS: The polymorphisms in the 3'UTR of the GRP78 gene are not correlated with the risk of male asthenozoospermia.