The insulin polymorphism -23Hph increases the risk for type 1 diabetes mellitus in the Romanian population

The insulin -23Hph and IGF2 Apa polymorphisms were genotyped in Romanian patients with T1DM (n = 204), T2DM (n = 215) or obesity (n = 200) and normoponderal healthy subjects (n = 750). The genotypes of both polymorphisms were distributed in concordance with Hardy-Weinberg equilibrium in all groups. The -23Hph AA genotype increased the risk for T1DM (OR: 3.22, 95%CI: 2.09-4.98, p < 0,0001), especially in patients without macroalbuminuria (OR: 4.32, 95%CI: 2.54-7.45, p < 0,0001). No other significant association between the alleles or genotypes of insulin -23Hph and IGF2 Apa and diabetes or obesity was identified.     

Association of a variant in exon 31 of the sulfonylurea receptor 1 (SUR1) gene with type 2 diabetes mellitus in French Caucasians

The sulfonylurea receptor (SUR1) of the pancreatic beta-cell ATP-sensitive potassium channel plays a key role in glucose-induced insulin secretion. The A-allele of a single nucleotide polymorphism (SNP) in exon 31 of the SUR1 gene (AGG-->AGA; Arg1273Arg) has previously been shown to be associated with hyperinsulinemia in nondiabetic Mexican-American subjects. Here, we have investigated the association of this SNP with type 2 diabetes mellitus (T2DM) in French Caucasian subjects. We have observed an increased frequency of the A allele (37.1% vs 27.6%, P=0.0048; odds ratio 1.54), of the AA genotype (15.7% vs 9.8%; P=0.025), and of the combined AA/AG genotypes (58.5% vs 45.5%, P=0.0098; odds ratio 1.69) in patients compared with controls. This association is stronger in the subgroup of patients with age of diagnosis of diabetes equal to or less than 45 years: A allele 43.2% (P=0.0003 compared with controls; odds ratio 1.99), AA genotype 21.4% (P=0.0032), and combined AA/AG genotypes 65.1% (P=0.0022; odds ratio 2.23). Unexpectedly, the G allele is strongly associated with arterial hypertension in obese diabetic subjects (GG vs AA odds ratio 19.97). In conclusion, we have observed an association of an SNP in exon 31 of the SUR1 gene with T2DM. These data reinforce the hypothesis that insulin secretion defects in T2DM might be at least partially related to allelic variations in the SUR1 gene.     

Study of Five Pubertal Transition-Related Gene Polymorphisms as Risk Factors for Premature Coronary Artery Disease in a Chinese Han Population

Background

Recently, single nucleotide polymorphisms (SNPs) (DLK-rs10144321, SIX6-rs1254337, MKRN3-rs12148769, LIN28B-rs7759938, and KCNK9-rs1469039) were found to be strongly associated with age at menarche. Recent studies also suggested that age at menarche is a heritable trait and is associated with risks for obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and all-cause mortality. Since an association between these five SNPs and premature coronary artery disease (CAD) has never been reported, we investigated whether these SNPs are associated with premature CAD and its severity in a Chinese Han population.

Methods

We enrolled 432 consecutive patients including 198 with premature CAD (<55 years in men and <65 years in women) and 234 controls. All subjects were genotyped for the five SNPs by the PCR-ligase detection reaction method. The associations between these SNPs and premature CAD and its severity were analyzed.

Results

The following genotypes were identified: GG, AG, and AA at rs10144321 and rs12148769; TT, AT, and AA at rs1254337; CC, CT, and TT at rs1469039; and TT and CT at rs7759938. Significant differences in genotype distribution frequencies at rs1254337 were found between controls and patients with premature CAD (P<0.05). No associations were found between the five SNPs and the severity of coronary lesions (all P>0.05). Compared with controls, patients with premature CAD had a higher prevalence of T2DM and dyslipidemia, and the proportion of patients with T2DM rose significantly with an increase in the number of stenosed coronary vessels (all P<0.05). After adjustment for the clinical parameters in multivariable analysis, three factors were identified that significantly increased the risk of premature CAD: the AA genotype at rs1254337 (OR: 2.388, 95% CI: 1.190–4.792, P = 0.014), male gender (OR: 1.565, 95% CI: 1.012–2.420, P = 0.044), and T2DM (OR 2.252, 95% CI: 1.233–4.348, P = 0.015).

Conclusions

Among the five pubertal transition-related gene polymorphisms, we identified an association between rs1254337 and premature CAD in a Chinese Han population.     

Association of VDR-gene variants with factors related to the metabolic syndrome,type 2 diabetes and vitamin D deficiency

The prevalence of metabolic syndrome (MetS) is rising alarmingly in the Saudi Arabian population. This study was conducted to assess the association between vitamin D receptor (VDR) polymorphisms and genetic susceptibility to components of the metabolic syndrome, type 2 diabetes mellitus (T2DM), and vitamin D deficiency in the Saudi Arabian population. Five-hundred-seventy Saudi individuals (285 MetS and 285 controls) were enrolled in this cross-sectional study. TaqI, BsmI, ApaI and FokI single nucleotide polymorphisms (SNPs) of the VDR gene were genotyped. The CT genotype and allele T of BsmI were associated with lower HDL-C levels [OR 0.60 (0.37, 0.96), p = 0.03] and obesity [OR 1.4 (1.0, 1.90), p = 0.04], respectively. The CT genotype and the dominant model CT + TT of BsmI were associated with increased risk of diabetes [OR 1.7 (1.2, 2.4), p = 0.007], and [OR 1.5 (1.1, 2.2), p = 0.01], respectively. On the contrary, the CT and CT + CC genotypes of FokI exhibited an association with a reduced risk of diabetes [OR 0.70 (0.49, 0.99), p = 0.05] and [OR 0.67 (0.48, 0.94), p = 0.02], respectively. The allele C of FokI was associated with lower risk of developing T2DM [OR 0.73 (0.56, 0.95), p = 0.02]. The prevalence of vitamin D deficiency was lower in subjects with the AC genotype of ApaI [OR, 0.34 (0.14, 0.80), p = 0.01]. Components of the MetS such as obesity, low HDL and T2DM were associated with the VDR gene. FokI and BsmI have protective and facilitative effects on the risk for T2DM, while the ApaI genotype was associated with reduced vitamin D deficiency.     

Potential risk modifications of GSTT1, GSTM1 and GSTP1 (glutathione-S-transferases) variants and their association to CAD in patients with type-2 diabetes

Background

Type-2 diabetes mellitus (T2DM) is a major risk factor for coronary artery disease (CAD) resulting in high morbidity and mortality. Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) are known for their broad range of detoxification and in the metabolism of xenobiotics. Recent studies revealed the relationship of GSTs variants with T2DM and CAD. In this case-control study we ascertained the association of GSTs variants in association with the development of CAD in patients with T2DM.

Methods

From the Southern part of India, we enrolled 222 T2DM patients, 290 T2DM patients with CAD and 270 healthy controls matched for age, sex and origin. Serum lipid profiles were measured and DNA was extracted from the blood samples. Multiplex PCR for GSTM1/T1 (null polymorphism) and PCR-RFLP for GSTP1 (105 A > G), were performed for genotyping of study participants. Gene frequency and lipid profiles were statistically analyzed for disease association.

Results

Regression analysis showed that, GSTM1-null genotype is associated with a 2-fold increase (OR = 2.925; 95% CI = 2.078–4.119; P < 0.0001) and GSTT1-null genotype is associated with a 3-fold increase (OR = 3.114; 95% CI = 2.176–4.456; P < 0.0001) to T2DM development. Ile/Val and Val/Val genotypes of GSTP1 also showed a significant risk for T2DM (OR = 1.423, CI = 1.041–1.946; P = 0.027 and OR = 1.829, CI = 1.064–3.142; P = 0.029). Increased odds ratio showed that GSTT1-null genotype had a moderately higher occurrence in T2DM–CAD patients (OR = 1.918, 95% CI = 1.144–3.214; P = 0.014) than T2DM patients without CAD. The level of HDL has significantly decreased in GSTT1-present than in GSTT1-null genotype (43.50 ± 4.10 vs. 45.20 ± 3.90; P = 0.004) when compared with control and T2DM patients. However, LDL level showed a significant increase in GSTT1-null than GSTT1-present genotype (108.70 ± 16.90 vs. 102.20 ± 12.60; P = 0.005). Although the GSTM1-null polymorphism showed no correlation with lipid profiles among T2DM and T2DM with CAD patients, GSTT1-null polymorphism attained a statistical significance for the level of LDL (127 ± 28.20 vs. 134 ± 29.10; P = 0.039) and triglycerides in T2DM with CAD patients (182.10 ± 21.10 vs. 191.20 ± 24.10; P = 0.018).

Conclusion

Our work concludes that GSTM1, GSTT1 and GSTP1 variants might contribute to the development of T2DM and GSTT1 variant alone is involved in the development of T2DM associated CAD complications in the South Indian population.     

白介素-10-819 C/C和肿瘤坏死因子-α-1031 C/C/基因型与胃十二指肠疾病易感性的关系

目的分析人群中IL-10-819 C/C和TNF-α-1031 C/C基因型与胃十二指肠疾病的关系,确定携带以上该基因型的的人群罹患胃十二指肠疾病易感性的风险性。为临床诊断和预防这些疾病提供新的思路和方法。方法选取H.pylori阳性的48例慢性胃炎患者,46例十二指肠溃疡患者,51例胃溃疡患者,43例胃癌患者和100例健康对照者,2种基因型分别采用普通PCR和多重引物特异PCR法检测。结果在胃炎组中TNF-A-1031各基因型的频率(T/T,50%;T/C,40%;C/C,10%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.975,P0.05)。在胃溃疡组中TNF-A-1031各基因型的频率(T/T,49%;T/C,43%;C/C,8%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.464,P0.001)。在十二指肠溃疡组中TNF-A-1031各基因型的频率(T/T,72%;T/C,26%;C/C,2%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.840,P0.05)。在胃癌组中TNF-A-1031各基因型的频率(T/T,50%;T/C,41%;C/C,9%)与对照组(T/T,73%;T/C,25%;C/C,2%)比较,分布差异有统计学意义(χ2=9.335,P0.001);Logistic回归分析与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃炎的危险性为OR=7.60(95%CI:1.38-41.77);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃溃疡的危险性为OR=5.84(95%CI:1.00-33.84);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生十二指肠溃疡的危险性为OR=7.94(95%CI:1.44-43.67);与携带TNF-A-1031 T/T者比较,携带TNF-A-1031 C/C者发生胃癌的危险性为OR=6.95(95%CI:1.19-40.63)。在疾病组和对照组中IL-10-819的各基因型频率的分布差异无统计学意义(P0.05)。结论 TNF-α-1031基因多态性与胃炎、胃溃疡、十二指肠、胃癌的易感性相关。     

SUMO4基因多态性与2型糖尿病的关系

为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4,SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus,T2DM)的关系,文章采用病例对照设计,选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象,应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法,检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况,比较T2DM组糖化血红蛋白(Hemoglobin A1c,HbA1c)在各基因型间的分布,并进行单倍型分析。结果显示:①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs.0.282,P=0.017);GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001;OR,1.563;95%CI,1.189-2.053);在显性模型(GG+GA vs.AA)分析中,G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P=0.002;OR,1.525;95%CI,1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P>0.05)。②在T2DM组,rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA1c水平,但各基因型携带者之间HbA1c水平并无统计学差异(P>0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1);而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论:rs237025多态性与北京汉族人群T2DM的易感性相关,rs237024和rs600739多态性可能与T2DM的易感性不相关。     

SUMO4基因多态性与2型糖尿病的关系

为了探讨北京汉族人群小泛素样修饰蛋白4(Small ubiquitin-like modifier 4, SUMO4)基因多态性与2型糖尿病(Type 2 diabetes mellitus, T2DM)的关系, 文章采用病例对照设计, 选取404例T2DM患者(T2DM组)以及年龄、性别匹配的500例健康对照者(Control组)作为研究对象, 应用聚合酶链反应-高分辨熔解曲线(PCR-HRM)技术结合测序验证法, 检测SUMO4基因3个单核苷酸多态性位点(rs237025、rs237024及rs600739)的基因型与等位基因分布情况, 比较T2DM组糖化血红蛋白(Hemoglobin A_1c, HbA_1c)在各基因型间的分布, 并进行单倍型分析。结果显示：①rs237025的G等位基因在T2DM组出现的频率更高(0.334 vs. 0.282, P =0.017); GA基因型携带者患T2DM的风险是AA基因型携带者的1.563倍(P=0.001; OR, 1.563; 95% CI, 1.189-2.053); 在显性模型(GG+GA vs. AA)分析中, G等位基因携带者(GG+GA)患T2DM的风险是AA基因型携带者的1.525倍(P =0.002; OR, 1.525; 95% CI, 1.169-1.989)。而rs237024和rs600739多态性未发现与T2DM的易感性相关(P >0.05)。②在T2DM组, rs237025的G等位基因携带者、rs237024的TT基因型携带者及rs600739的GG基因携带者具有较高的HbA_1c水平, 但各基因型携带者之间HbA_1c水平并无统计学差异(P >0.05)。③单倍型AAC、AGC及GGT与T2DM的易感性正相关(OR>1); 而单倍型AAT、GAC与T2DM的易感性负相关(OR<1)。据此得出结论：rs237025多态性与北京汉族人群T2DM的易感性相关, rs237024和rs600739多态性可能与T2DM的易感性不相关。     

Genetic association of Glutathione peroxidase-1 (GPx-1) and NAD(P)H:Quinone Oxidoreductase 1(NQO1) variants and their association of CAD in patients with type-2 diabetes

Coronary artery disease (CAD) is a major health concern and the leading cause of death in individuals with type-2 diabetes mellitus (T2DM). Glutathione peroxidase-1 (GPx-1) and NAD(P)H: quinone oxidoreductase (NQO1) are known for its broad range of detoxification. The role of functional variants of these genes in the development of various disorders is proven. Hereby, we investigated the possible role of these variants in the development of CAD in T2DM patients of South Indian population. In this case-control study, a total of 539 patients (T2DM = 241; T2DM-CAD = 298) and 285 controls were included. The C198T GPx-1 and C609T NQO1 single-nucleotide polymorphisms were analyzed by PCR-RFLP. Further, these genotypes were correlated with blood lipid profile. Regression analysis showed that GPx1-C/T genotype is associated with a 1.35-fold increase (95% CI = 1.000-1.824; P = 0.048) and GPx1-T/T genotype is associated with a 1.76-fold increase (95% CI = 1.011 to 3.066; P = 0.046) to the T2DM development. Increased odds ratio showed that NQO1-T/T genotype had a higher occurrence of CAD in diabetic patients with CAD (95% CI = 1.003-2.674, P = 0.049) than T2DM patients without CAD. The level of triglycerides alone showed significant increase for GPx-1-C/T and -T/T genotypes in Tukey's Post hoc analysis (177.1 ± 19.2 vs. 184 ± 23.5; P = 0.039 and 177.1 ± 19.2 vs. 190 ± 22.4; P = 0.006) among the patients with T2DM-CAD. Our work concludes that GPx-1 variants might contribute to the development of diabetes and both GPx-1 and NQO1 variants confirm the association of CAD in people with T2DM of South Indian population.     

Associations between tumor necrosis factor alpha gene polymorphism and sarcoidosis: a meta-analysis

Published studies regarding the association between tumor necrosis factor alpha (TNF-α) gene polymorphism and sarcoidosis risk are inconsistent. In order to clarify this association, we performed a meta-analysis of case–control studies with available data. PubMed, EMBASE and BIOSIS Previews were comprehensively searched to identify relevant studies. Twelve case–control studies in 11 articles involving 3,218 participants were included in the meta-analysis to assess the association between TNF-α gene polymorphism and susceptibility to sarcoidosis. We estimated the pooled odds ratio (OR) with its 95 % confidence intervals (95 % CI) to explore the potential association. Our meta-analysis results suggested that TNF-α-308G/A AA/AG genotype increased sarcoidosis risk, in Asian and Caucasian ethnicity, and in sarcoidosis with Löfgren syndrome. No association was found between TNF-α-238G/A, TNF-α-857C/T polymorphism and sarcoidosis risk. In conclusion, our meta-analysis indicated that AG/GG genotype of TNF-α-308G/A are associated with increased sarcoidosis risk.     

rs4215 SNP in zinc-α2-glycoprotein gene is associated with obesity in Chinese north Han population

Objective

Zinc-α2-glycoprotein (ZAG) has been identified recently as a novel adipokine due to its close link with lipid and glucose metabolism, as well as regulation of body weight. The aim of our present study is to investigate the ZAG genetic polymorphism association with obesity in Chinese north Han population.

Design and methods

Five SNPs of ZAG gene including rs2247607 (A>T), rs4727442 (G>T), rs4215 (A>G), rs2527923 (C>T) and rs2527882 (C>T) were genotyped in 648 overweight/obese patients and 313 healthy controls by TaqMan-PCR methods. Crosstabs statistical analysis method with subjects stratifying by age (≦ 30 y, 31–45 y, ≧ 46 y) and gender was used.

Results

The results showed the constitution of three genotype frequencies in rs4215 (A>G) site significantly differs in male subgroup (aged 31–45 y) between overweight/obese and healthy control group (χ² = 6.401, P = 0.041). GG genotype frequency in overweight/obese group is 19.3% which is much higher than 6.1% in healthy control group. Further statistical analysis under a recessive inheritance model demonstrated odd ratio (OR) for GG vs. AA+AG in overweight/obese group was 3.674 (95% CI 1.049–12.866; P = 0.035). Among three genotypes of rs4215, the subjects with GG genotype have much more higher body weight, BMI, waist circumference and SBP.

Conclusion

Our data, for the first time, suggest the genotypes of rs4215 in ZAG gene are significantly associated with obesity in Chinese north Han population. GG genotype subjects in rs4215 site have an increased susceptibility to obesity when compared with the AA+AG genotype subjects.     

The 712A/G polymorphism of Brain-derived neurotrophic factor is associated with Parkinson's disease but not Major Depressive Disorder in a Chinese Han population

Background: Overlaps in clinical, pathological and molecular characteristics of Parkinson’s disease (PD) and Major Depressive Disorder (MD-D) have promoted association studies in search of common genetic risk factors that may predispose or modify this spectrum of disorders. Experimental and clinical data suggest that genetic variations in Brain-derived neurotrophic factor (BDNF) gene may increase the risk for PD and MD-D. Methods: Two hundred and sixty-six PD, 83 MD-D and 400 controls were recruited for this study, assessed using a battery of neuropsychological tests, and genotyped for 11757C/G, 712A/G, 196A/G, and 270C/T in BDNF gene. Results: 712A/G was associated with 2.50-fold time risk of PD. By combining genotypes AG/AA with 712 GG genotype as reference (OR = 1) in stratification analysis, AG/AA genotypes were associated with PD (OR = 2.94, 95% CI = 1.88–4.61). Accordingly, the A allele was significantly overrepresented in PD compared with the G allele (OR = 3.16, 95% CI = 2.08–4.81). This distribution in females and males were similar. Conclusion: Our results suggested a novel association between BDNF 712A/G AG/AA genotypes and PD in a Chinese Han population.     

白介素-1和肿瘤坏死因子-α基因多态性与幽门螺杆菌相关性胃十二指肠疾病的关系

目的探讨汉族人群中IL-1和TNF-α基因多态性与H.pylori相关性胃十二指肠疾病之间的关系。方法选取H.pylori阳性的142例胃十二指肠疾病患者和140例健康对照者,采用PCR-限制性长度片段多态方法检测该人群中IL-1B-511、TNF-A-308、TNF-A-857位点多态性和IL-1受体拮抗剂基因的多态性。结果 IL-1B-511和IL-1RN各基因型的频率在疾病组和对照组中的分布差异无统计学意义。在疾病组中TNF-A-308和TNF-A-857各基因型的频率与对照组比较,分布有差异,具有统计学意义(P0.05)。经Logistic回归分析,与携带TNF-A-308G/G者比较,携带TNF-A-308 A/A者发生胃十二指肠疾病的危险性为OR=15.37(95%CI:3.50-67.50);携带TNF-A-308 A/G者发生胃十二指肠疾病的危险性为OR=5.12(95%CI:2.54-10.34);与携带TNF-A-857 C/C者相比较,携带TNF-A-857 T/T者发生胃十二指肠疾病的危险性为OR=3.20(95%CI:1.35-7.60)。结论 IL-1B-511和IL-1RN各基因型与幽门螺杆菌相关性胃十二指肠疾病的发生不相关。TNF-α基因多态性与幽门螺杆菌相关性胃十二指肠疾病的发生相关。     

脂联素基因单核苷酸多态性与Ⅱ型糖尿病合并肥胖及胰岛素抵抗相关联

脂联素是近年新发现的脂肪组织特异性的细胞因子,其mRNA是脂肪组织中含量最丰富的基因转录产物,该因子可通过多种途径影响个体对胰岛素的敏感性。脂联素基因多态性与肥胖、胰岛素抵抗和2型糖尿病密切相关,而与冠心病相关性研究的报道较少。本研究以中国汉族人群1,098例为对象,其中304例冠心病(CHD)患者,389例糖尿病患者(T2DM),及405例性别年龄相匹配的正常对照,采用PCR-RFLP技术对脂联素基因-4522C/T进行基因分型,并分别对血脂水平、胰岛素抵抗、体重指数等临床数据进行分析比较。研究结果显示,脂联素基因-4522C/T各基因型及等位基因在CHD组与对照组、T2DM组与对照组中的分布差异无显著性;经分组分析发现,T2DM合并肥胖患者BMI≥25kg/m2TT基因型及T等位基因明显多于对照组,差异有显著性,P=0.014和P=0.034;TT基因型T2DM患者胰岛素抵抗指数(HOMA-IR)显著高于携带有C等位基因的T2DM患者,P=0.0069。本研究提示脂联素基因-4522C/T与中国汉族人群T2DM合并肥胖的发生及T2DM患者胰岛素抵抗相关,是引发糖尿病患者肥胖和胰岛素抵抗的重要候选基因,而与冠心病的发生无关联。     

TNF-alpha −308G/A and −238G/A polymorphisms and its protein network associated with type 2 diabetes mellitus

Several reports document the role of tumor necrosis factor alpha (TNF-α) and lipid metabolism in the context of acute inflammation as a causative factor in obesity-associated insulin resistance and as one of the causative parameter of type 2 diabetes mellitus (T2DM). Our aim was to investigate the association between −308G/A and −238G/A polymorphisms located in the promoter region of the TNF-α gene in T2DM in the Indian population with bioinformatics analysis of TNF-α protein networking with an aim to find new target sites for the treatment of T2DM. Demographics of 100 diabetes patients and 100 healthy volunteers were collected in a structured proforma and 3 ml blood samples were obtained from the study group, after approval of Institutional Ethics Committee of the hospital (IEC). The information on clinical parameters was obtained from medical records. Genomic DNA was extracted; PCR–RFLP was performed using TNF-α primers specific to detect the presence of SNPs. Various bioinformatics tools such as STRING software were used to determine its network with other associated genes. The PCR–RFLP studies showed that among the −238G/A types the GG genotype was 87%, GA genotype was 12% and AA genotype was 1%. Almost a similar pattern of results was obtained with TNF-α −308G/A polymorphism. The results obtained were evaluated statistically to determine the significance. By constructing TNF-α protein interaction network we could analyze ontology and hubness of the network to identify the networking of this gene which may influence the functioning of other genes in promoting T2DM. We could identify new targets in T2DM which may function in association with TNF-α. Through hub analysis of TNF-α protein network we have identified three novel proteins RIPK1, BIRC2 and BIRC3 which may contribute to TNF-mediated T2DM pathogenesis. In conclusion, our study indicated that some of the genotypes of TNF-α −308G/A, −238G/A were not significantly associated to type 2 diabetes mellitus, but TNF-α −308G/A polymorphism was reported to be a potent risk factor for diabetes in higher age (>45) groups. Also, the novel hub proteins may serve as new targets against TNF-α T2DM pathogenesis.     

Association between the −1438G/A and T102C polymorphisms of 5-HT2A receptor gene and obstructive sleep apnea: a meta-analysis

The serotonin 2A (5-HT2A) receptor has been implicated in obstructive sleep apnea (OSA). Single nucleotide polymorphisms (SNPs) in the 5-HT2A gene have been found in OSA, the most common being ?1438G/A and T102C; however, studies of the association between 5-HT2A SNPs and OSA risk have reported inconsistent findings. A meta-analysis was performed to quantitatively review the association between ?1438G/A and T102C SNPs and OSA. Five studies, including 791 subjects for ?1438G/A genotype and 1,068 subjects for T102C genotype, were selected. Pooled data analysis of the ?1438G/A genotype indicated a significantly increased OSA risk was associated with two variant genotypes (AA vs. AG+GG: OR 3.023, 95 % CI 2.169–4.213, P = 0.506 for heterogeneity; A allele carriers vs. GG: OR 1.938, 95 % CI 0.879–4.274, P = 0.012 for heterogeneity). Stratification analysis by gender supported the association in males, but not females. For the T102C genotype, no significantly increased OSA risk was associated with the two variant genotypes (CC vs. CT+TT: OR 1.065, 95 % CI 0.787–1.442, P = 0.361 for heterogeneity; C allele carriers vs. TT: OR 0.979, 95 % CI 0.737–1.3, P = 0.9 for heterogeneity).In conclusions, meta-analysis indicated that the ?1438G/A, and not T102C, polymorphism of 5-HT2A is a positive risk factor of OSA, especially in males.     

Assessment of 11-β hydroxysteroid dehydrogenase (11-βHSD1) 4478T>G and tumor necrosis factor-α (TNF-α)-308G>A polymorphisms with obesity and insulin resistance in Asian Indians in North India

11-β hydroxysteroid dehydrogenase (11-βHSD1), tumor necrosis factor-α (TNF-α) and their role in obesity, regional adiposity and insulin resistance has been sparsely evaluated. We determined the polymorphic status of 11-βHSD1 4478T>G and TNF-α-308G>A in Asian Indians in north India. In this cross-sectional study (n = 498; 258 males, 240 females), association of genotypes (PCR–RFLP) of 11-βHSD1 and TNF-α were analyzed with obesity [BMI ≥ 25 kg/m², percentage body fat (%BF by DEXA); subcutaneous and intra-abdominal fat area (L_2–3 level by single slice MRI) in a sub sample] and insulin resistance. 46 percent subjects had generalized obesity, 55 % abdominal obesity and 23.8 % were insulin resistant. Frequencies (%) of [T/T] and [T/G] genotypes of 11-βHSD1 were 89.57 and 10.43 respectively. Homozygosity for 11-βHSD1 4478G/G was absent with no association with parameters of obesity and insulin resistance. Frequencies (%) of TNF-α [G] and [A] alleles were 88 and 12 respectively. Higher frequency of variant -308[A/A] was observed in females versus males (p = 0.01). Females with at least one single A allele of TNF-α-308G>A had significantly high %BF and total skinfold, whereas higher values of waist hip ratio, total cholesterol, triglycerides and VLDL were observed in males. Subjects with even a single A allele in TNF-α genotype showed higher subscapular skinfold predisposing them to truncal subcutaneous adiposity (p = 0.02). Our findings of association of TNF-α-308G>A variant in females with obesity indices suggests a gender-specific role of this polymorphism in obesity. High truncal subcutaneous adiposity is associated with A allele of TNF-α-308G>A in this population.     

Association of TNF-α and IL-10 polymorphisms with tuberculosis in Tunisian populations

Cytokine Th1/Th2 balance is known to play a key role in controlling Mycobacterium tuberculosis infection. Based upon the functional role of the TNF-α [-308 G(low)?→?A(high) (rs1800629)] and IL-10 [-1082 A(low)?→?G(high) (rs1800870), -819 T(low)?→?C(high) (rs1800871) and -592 A(low)?→?C(high) (rs1800872)] single nucleotide polymorphisms (SNPs) on production levels, we genotyped 76 patients with pulmonary tuberculosis (TB) (pTB), 55 patients with extrapulmonary TB (epTB) and 95 healthy blood donors by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that -308 A allele was associated with increased risk susceptibility to epTB (OR?=?1.96; 95% CI, 1.04-3.71; P?=?0.024). The -1082 AG genotype was significantly associated with increased risk development of epTB (odds ratio [OR]?=?3.69; 95% confidence intervals [CI], 1.73-7.92; P corrected for the number of genotypes [Pc]?=?0.0003). By contrast, -1082 AA genotype appeared to be associated with resistance to pTB (OR?=?0.38; 95% CI, 0.19-0.74; Pc?=?0.006) and epTB (OR?=?0.22; 95% CI, 0.1-0.48; Pc?=?0.00006). High-producer IL-10 GCC haplotype seemed to be associated with 2.11-fold (95% CI, 1.28-3.46; Pc?=?0.003) and 2.57-fold (95% CI, 1.5-4.4; Pc?=?0.0006) increased susceptibility to pTB and epTB, respectively. Combination of TNF-α/IL-10 high producer genotypes was associated with increased 3.13-fold (95% CI, 1.23-8.05; Pc?=?0.028) susceptibility to epTB. However, combined TNF-α/IL-10 low producer genotypes appeared to have protect effect to pTB (OR?=?0.44, 95% CI, 0.21-0.89; Pc?=?0.04) and epTB (OR?=?0.26, 95% CI, 0.1-0.62; Pc?=?0.0028). Collectively, our results showed that analysed SNPs in the TNF-α and IL-10 gene polymorphisms play key role in susceptibility to or protection against TB development in Tunisian populations.     

Associations of fibroblast growth factor 21 gene 3' untranslated region single-nucleotide polymorphisms with metabolic syndrome, obesity, and diabetes in a Han Chinese population

Fibroblast growth factor 21 (FGF-21) is a novel regulator for metabolic syndrome (MetS), diabetes, and obesity. However, no study has been performed on the association of these diseases with FGF-21 gene polymorphism. The aim of the study was to investigate the association of 3' untranslated region (UTR) single-nucleotide polymorphisms (SNPs) in the FGF-21 gene with MetS, obesity, and diabetes in the Han Chinese population. A total of 291 subjects were recruited from the Han Chinese population in Sichuan province. The genotypes of FGF-21 were determined by polymerase chain reaction-restriction fragment length polymorphism. The genotypes were confirmed by sequencing. No polymorphisms were found in rs11665841 (1 of 291) and rs3745706 (2 of 291). We did not find an association between genotype frequencies of SNP rs11665896 and lipid concentration, glucose concentration, or blood pressure. The TG/GG genotype relative to the TT genotype had an age- and sex-adjusted odds ratio of 1.41 for MetS (p=0.149), 1.84 (p=0.016) for obesity (body mass index ≥25?kg/m(2)), and 1.19 (p=0.492) for diabetes. Genetic variation of the 3' UTR of the FGF-21 gene was associated with obesity, however, not with MetS or diabetes.