Combination of CTLA-4 and TGFβ1 gene polymorphisms associated with dengue hemorrhagic fever and virus load in a dengue-2 outbreak

The pathogenesis of dengue hemorrhagic fever (DHF) has been considered to be massive immune activation of T cells. Abnormal expression of the immune regulatory molecules, CTLA-4 and TGFβ1, leads to disturbances of regulatory T cell immune response. We investigate the contribution of CTLA-4 and TGFβ1 in DHF by analyzing them for association with virus load in blood and polymorphisms of CTLA-4 +49A/G, and TGFβ1 −509C/T in a DEN-2 outbreak. The increased frequency of the TGFβ1 −509 CC genotype in patients with DHF was compared to those with dengue fever (OR = 1.9, p = 0.034). Moreover, the presence of the CTLA-4 +49 G allele and TGFβ1 −509 CC genotype increased the susceptibility to risk of DHF (OR = 2.1, p = 0.028) and significantly higher virus load (p = 0.013). This finding suggests that a combination of CTLA-4 and TGFβ1 polymorphisms is associated with the susceptibility of DHF and higher virus load.     

Vascular endothelial growth factor gene polymorphisms and vasculitis susceptibility: A meta-analysis

Objective

The aim of this study was to explore whether vascular endothelial growth factor (VEGF) polymorphisms are associated with susceptibility to vasculitis.

Methods

Meta-analyses were conducted on the associations between the −634 C/G, +936 C/T, −1154 A/G, and −2578 A/C polymorphisms of VEGF and vasculitis.

Results

Eight studies on VEGF polymorphisms and vasculitis involving 2740 subjects (vasculitis 834, controls 1906) were included in this meta-analysis. The meta-analysis showed no association between vasculitis and the VEGF −634 C allele (OR = 1.161, 95% CI = 0.921–1.464, p = 0.207) among study subjects. Meta-analysis showed no association between vasculitis and the VEGF + 936 T allele (OR = 1.121, 95% CI = 0.905–1.390, p = 0.295). However, stratification by ethnicity indicated a significant association between the VEGF + 936 T allele and vasculitis in Europeans, but not in Asians (OR = 1.486, 95% CI = 1.038–2.128, p = 0.030; OR = 0.958, 95% CI = 0.773–1.253, p = 0.755). Meta-analysis showed no association between vasculitis and the VEGF −1154 A/G and 2578 A/C polymorphisms.

Conclusions

This meta-analysis suggests that the VEGF + 936 T allele is associated with susceptibility to vasculitis in Europeans, but not in Asians.     

Impact of VEGF polymorphisms on the severity of peripheral artery disease in diabetic patients

Objective. To determine the potential genotype vascular endothelial growth factor (VEGF) gene differences in diabetic patients with peripheral arterial disease (PAD), which might be associated with different stages of the vascular disease. Methods. A study was conducted with type 2 diabetic patients with PAD [n = 70; 32 intermittent claudication and 38 critical limb ischaemia (CLI)]. Genotyping of the VEGF gene insertion/deletion ? 2549, ? 2578 C/A and +405 G/C polymorphisms was done in both groups and correlated them with the severity of PAD. We compared serum VEGF levels in both groups. Results. There was a higher frequency of +405 CC and ? 2578 CC genotypes in claudication group [(31.3% vs. 5.4%, p = 0.01) and (37.5% vs. 15.8%, p = 0.05), respectively]. The presence of +405 GG and ? 2578 AA genotypes was more common among CLI patients [(57.8% vs. 37.5%, p = 0.01) and (42.1% vs. 18.8%, p = 0.05), respectively]. There were higher serum VEGF levels in patients with CLI (p = 0.029). Conclusions. We found preliminary evidence regarding the association between VEGF polymorphisms and different stages of PAD in diabetic patients.     

−1154G/A and −2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to β-amyloid (1–42) and total tau protein

Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (−2578C/A) and (−1154G/A) polymorphisms did not differ significantly between AD and control groups (p > 0.05). In the subgroup of ApoE ?4 carriers, the −2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE ?4 status using logistic regression, the −2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the −2578A allele may be associated with the development of AD in the individuals with ApoE ?4 allele. In addition, AD patients carrying the −2578A allele had lower Aβ42 (p = 0.029) levels than those without this allele, particularly in subjects with ApoE ?4 allele.     

Gene polymorphisms of interleukin-4, interleukin-10 and transforming growth factor-beta in Graves’ disease

Among genetic factors that may contribute to the development and progression of Graves’ disease (GD) and its complications are polymorphisms in the genes encoding cytokines. The association between GD and the following polymorphisms in anti-inflammatory cytokines was studied in 107 patients with GD and 140 healthy controls: IL-4 (−1098T/G, −590T/C, −33C/T), IL-10 (−1082A/G, −819C/T, −592C/A) and TGF-β (+869T/C, +915G/C). The following alleles and genotypes were significantly (P < 0.01 after correction for multiple testing) more frequent among patients: the IL-4 −1098G allele and GG genotype (OR = 3.12 and 105.00, respectively), IL-4 −33T allele and TT genotype (OR = 2.52 and 118.83, respectively), IL-10 −1082G allele and GG genotype (OR = 2.16 and 6.40, respectively), IL-10 −819T allele, TC and TT genotype (OR = 2.60, 3.68 and 6.76, respectively), IL-10 −592A allele, AC and AA genotype (OR = 2.41, 2.89 and 5.68, respectively), TGF-β +869C allele and CC genotype (OR = 2.24 and 6.21, respectively), and TGF-β +915C allele, CG and CC genotype (OR = 7.81, 11.80 and 20.40, respectively). The only allele and genotype with a lower frequency in patients were IL-4 −590T allele and TC genotype (OR = 0.47 and 0.08, respectively; P < 0.01). In conclusion, this study highlighted the importance of anti-inflammatory cytokine gene polymorphisms in susceptibility to GD.     

Association between interleukin‐21 gene polymorphisms (rs12508721) and HBV‐related hepatocellular carcinoma

Interleukin‐21 (IL‐21), as a multifunctional cytokine, plays an important role in many diseases, such as cancer, inflammatory and autoimmune diseases. We aimed to investigate the relationship between polymorphisms of IL‐21 gene and susceptibility of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) in a Chinese population. Studied subjects were divided into three groups: 100 patients with HBV‐related HCC, 115 patients with chronic HBV infection and 127 healthy controls. Genomic DNA was isolated from peripheral blood, and the polymerase chain reaction–ligase detection reaction (PCR‐LDR) method was used to genotype the SNPs (rs2221903, rs907715 and rs12508721) within IL‐21 gene. Our results showed that IL‐21 polymorphisms were associated with the risk of HCC and chronic HBV infection when compared with healthy controls. The rs2221903A/G AG genotype was associated with a higher risk of chronic HBV infection when compared with healthy controls [AG versus AA + GG, P = 0.036, OR = 1.898, 95%CI = 1.038–3.471]. The rs12508721C/T TT genotype was related with a lower risk of chronic HBV infection and HBV‐related HCC than in healthy controls [TT versus CT + CC, P = 0.026, OR = 0.451, 95%CI = 0.221–0.920; P = 0.049, OR = 0.482, 95%CI = 0.231–1.005]. No significant difference in the genotype and allele distrubutions of rs907715G/A SNP was observed in the HBV‐related HCC group, chronic HBV‐infected group and the healthy control group when compared to each other. Our findings suggest that the rs12508721T/C and rs2221903A/G polymorphisms of IL‐21 gene are associated with the susceptibility of HBV‐related HCC and chronic HBV infection. The genetic variant may in fact cause protection against the HBV‐related HCC. However, the function in these SNPs of IL‐21 gene needs to clarify the mechanisms involved in the pathogenesis of HBV‐related HCC further.     

Interleukin 10 gene promoter polymorphisms (rs1800896, rs1800871 and rs1800872) and haplotypes are associated with the activity of systemic lupus erythematosus and IL10 levels in an Iranian population

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with unknown aetiology. According to the role of interleukin 10 (IL10) in SLE pathogenesis, the genetic alterations in its promoter region could be associated with elevated IL10 levels and exacerbated disease. Here, we investigated the association of genotype and haplotype frequencies of three IL10 gene promoter polymorphisms with susceptibility to SLE, IL10 plasma levels and disease activity of patients in an Iranian population. A total of 116 SLE patients and 131 healthy subjects were enrolled. The PCR‐RFLP technique was used to detect IL10 promoter genotypes at the positions of ?1082 (G/A), ?819 (C/T) and ?592 (C/A) in association with IL10 plasma levels and SLEDAI scores. The GG genotype of ?1082 polymorphism was associated with the increased risk of SLE [OR = 2.65, 95% CI (1.21–5.82), p‐value = 0.046]. The CC genotype in ?819 region was associated with SLE susceptibility [OR = 3.38, 95% CI (1.26–9.07), p‐value = 0.034] and C allele was introduced as risk allele [OR = 1.86, 95% CI (1.15–3.01), p‐value = 0.009] in this region. IL10 plasma levels were overexpressed in CC genotype carriers of ?592 SNP and decreased in AA genotype carriers of ?1082. IL10 was also increased in SLE patients with CGT (?592/?1082/?819) haplotype. The SLEDAI score was higher among CC genotype carriers at the position of ?592 and TT genotype carriers at the region of ?819. SLEDAI was also elevated among patients with CGC (?592/?1082/?819) and CAC (p = 0.011) haplotypes. The present study suggests that the IL10 –819(C/T), ?1082(G/A) and ?592(C/A) polymorphisms and the haplotypes are associated with SLE susceptibility, increased disease activity and elevated IL10 levels. While this is the first time to report such an association in an Iranian population, further studies are needed to confirm these findings.     

Vascular endothelial growth factor genotypes and haplotypes are associated with pre-eclampsia but not with gestational hypertension

Vascular endothelial growth factor (VEGF) is relevant for normalpregnancy, and abnormalities in VEGF functions are associatedwith hypertensive disorders of pregnancy. Because there arefew studies on how VEGF genetic polymorphisms affect susceptibilityto pre-eclampsia (PE), and no studies on how they affect susceptibilityto gestational hypertension (GH), we compared VEGF genotypeand haplotype distributions in normotensive and hypertensivepregnancies. Genotypes and haplotypes for VEGF polymorphisms(C-2578A, G-1154A and G-634C) were determined in 303 pregnantwomen (108 healthy pregnant, HP; 101 with GH and 94 with PE).When white and non-white pregnant women were considered together,no significant differences were found in the distributions ofVEGF genotypes or haplotypes (P > 0.05) in the three groups.However, with only white subjects, significant differences werefound in genotypes distributions for two (C-2578A and G-634C)VEGF polymorphisms (both P < 0.05) between the HP and thePE groups. Importantly, the haplotype including the variantsC-2578, G-1154 and C-634, which is associated with higher VEGFgene expression, was less common in the PE group compared withthe HP group (4% versus 16%; P = 0.0047). However, we foundno significant differences in VEGF haplotypes distributionswhen the HP and GH groups were compared (P > 0.05). Thesefindings suggest a protective effect for the ‘C-2578,G-1154 and C-634’ haplotype against the development ofPE, but no major effects of VEGF gene variants on susceptibilityto GH.     

Meta-analysis of FKBP5 gene polymorphisms association with treatment response in patients with mood disorders

The aim of our study was to assess the association between FKBP5 gene polymorphisms and treatment response in patients with mood disorders using a meta-analysis. Eight separate studies that included data from 2199 subjects were identified. Meta-analysis was performed for three FKBP5 gene polymorphisms (rs1360780, rs3800373, and rs4713916). A significant association of FKBP5 gene rs4713916 polymorphism and response rate was found in patients with mood disorders (Overall: A versus G: OR = 1.28, 95%CI = 1.06–1.53, P = 0.01; GA + AA versus GG: OR = 1.32, 95%CI = 1.05–1.67, P = 0.02. Caucasian: A versus G: OR = 1.28, 95%CI = 1.06–1.55, P = 0.01; GA + AA versus GG: OR = 1.33, 95%CI = 1.04–1.70, P = 0.02). However, we did not detect the association between FKBP5 gene rs1360780 and rs3800373 polymorphisms and treatment response in patients with mood disorders (P > 0.05). This meta-analysis demonstrates that treatment response in patients with mood disorders is associated with FKBP5 gene rs4713916 polymorphism, but not rs1360780 and rs3800373.     

Heterozygote AG variant of -596 A/G IL-6 gene polymorphism is a marker for cutaneous T-cell lymphoma (CTCL)

The aim of the study was to investigate possible associations of IL-6 gene polymorphisms (−596 A/G and −174 C/G) with cutaneous T-cell lymphoma (CTCL). In the case-control study, genotype distributions and allelic frequencies in two promoter IL-6 gene polymorphisms in the group of 63 Czech patients with CTCL were compared to those of 105 control non-CTCL subjects matched for age and sex. The IL-6 gene polymorphisms were determined by PCR with following restriction analysis. A significant difference of −596 A/G IL-6 genotype distribution was found between the CTCL patients and the controls (P = 0.002) with almost threefold odds ratio for the heterozygote (AG) genotype in CTCL patients (OR = 2.64, P = 0.002). No significant differences in genotype distribution and/or allelic frequency of functional −174 C/G IL-6 gene polymorphism were observed. The double heterozygote AGCG of both IL-6 promoter polymorphisms was associated with CTCL (OR = 2.24, 95% confidence interval 1.17–4.28, P = 0.01). Thus, the heterozygote variant of −596 A/G promoter IL-6 polymorphism could be considered as a genotype marker for CTCL.     

HLA‐G gene 14‐bp deletion variant protects Iranian subjects against chronic hepatitis B infection

To investigate whether 14‐bp Ins/Del polymorphism in HLA‐G gene is associated with the risk of chronic hepatitis B (CHB) infection. This study was performed on a total of 396 individuals including 199 CHB patients and 197 healthy subjects from a south‐east Iranian population. We genotyped 14‐bp Ins/Del polymorphism in the HLA‐G gene using polymerase chain reaction method. The results of our study revealed that the HLA‐G 14‐bp deletion polymorphism was associated with a reduced risk of CHB at both allele and genotypic levels. The 14‐bp Del allele and Ins/Del genotype were more frequent in control group than in CHB patients (37% vs 28% for Del allele with OR = 0.68 and p‐value = .015; 73% vs 52% for Ins/Del genotype with OR = 0.43 and p‐value = .001) and both were protective factors against CHB. However, no difference was found in the distribution of HLA‐G 14‐bp genotypes among subjects with varied levels of HBV DNA or hepatic enzymes (p > .05). Our findings, for the first time, suggest that the HLA‐G 14‐bp Ins/Del polymorphism may be a marker for genetic susceptibility to CHB infection.     

Association of cytokine Th2 gene polymorphisms with autoimmune thyroid diseases in Tunisian population

Autoimmune thyroid diseases (AITD) including Graves' disease (GD) and Hashimoto's thyroiditis (HT) are complex genetic diseases. Th2 cytokines act on the development of AITD. This study was conducted on Tunisian patients with AITD to investigate the association of Th2 cytokine gene polymorphisms and haplotype combination with GD or HT risk. A total of 156 controls, 160 patients with HT and 88 patients with GD were genotyped for IL‐4 rs2243250, IL‐5 rs2069812, IL‐6 rs1800796 and IL‐13 rs1800925 polymorphisms by PCR‐RFLP. The AITD risk was assessed by a logistic regression analysis using the SNP stats statistical program. False‐positive report probability (FPRP) was estimated to evaluate significant findings. IL‐13 rs1800925 was associated with GD, after adjustment for age and gender, in codominant, dominant and allele genetic models (p = .0072; p = .0018; p = .012, respectively). Significant association of the IL‐6 rs1800796C/G genotype with GD was also detected (p = .025). Furthermore, increased risk of HT was still found for IL‐13 rs1800925T allele (p = .039, OR = 1.39) and for IL‐4 rs2243250T/T genotype both in codominant (p = .033, OR = 2.59) and recessive (p = .011, OR = 2.73) models after adjustment for age and gender. Interestingly, haplotype analysis performed on the IL‐4, IL‐5 and IL‐13 genes revealed a high risk of HT with CTT haplotype (p = .008, OR = 2.12). However, the CCT haplotype is a protective factor (OR = 0.36). Patients carrying the CT haplotype with only one minor allele had a moderate risk of HT (OR = 1.56). The FPRP analysis showed that the association of IL‐13 rs1800925 polymorphism with GD and HT and the association of CTT haplotype with HT were noteworthy. In conclusion, the IL‐4, IL‐5, IL‐6 and IL‐13 polymorphism may play a role in susceptibility to GD and HT in the Tunisian population. Furthermore, gene–gene interaction between the IL‐4, IL‐5 and IL‐13 significantly increases the risk of AITD. Further studies with larger numbers of individuals are needed to confirm the results.     

Functional polymorphisms in CD86 gene are associated with susceptibility to pneumonia‐induced sepsis

Sepsis is an illness in which the body has a severe response to bacteria or other germs. A bacterial infection in the body such as lungs may set off the response that leads to the disease. CD86 (B7‐2) is expressed on various immune cells and plays critical roles in immune responses. Genetic polymorphisms in CD86 gene may affect the development of several diseases. Here, we evaluated the association between two CD86 polymorphisms (rs1915087C/T and rs2332096T/G) and susceptibility to pneumonia‐induced sepsis. CD86 rs1915087C/T and rs2332096T/G were identified in 186 pneumonia‐induced septic patients and 196 healthy controls in the Chinese population. Results revealed that subjects with rs1915087CT and TT genotypes had significantly lower risk of pneumonia‐induced sepsis than those with CC genotype [odds ratio (OR) = 0.58, 95% confidence interval (CI), 0.37–0.91, p = 0.017, and OR = 0.40, 95%CI, 0.21–0.76, p = 0.005]. However, prevalence of rs2332096GG genotype and G allele were significantly increased in patients than in healthy controls (OR = 2.75, 95%CI, 1.46–5.16, p = 0.001, and OR = 1.65, 95%CI, 1.21–2.24, p = 0.001]. We further investigated functions of these two polymorphisms by assessing gene expression in peripheral blood mononuclear cells and in monocytes. Data showed subjects carrying rs2332096GG genotype had significantly decreased level of CD86 in monocytes than those carrying rs2332096TT genotype. These results indicate that CD86 polymorphisms are associated with susceptibility to pneumonia‐induced sepsis and may affect gene expression in monocytes.     

Novel polymorphisms in the promoter and 5' UTR regions of the human vascular endothelial growth factor gene

We have characterized 5 novel, single-nucleotide polymorphisms in the promoter and 5′ UTR regions of the human vascular endothelial growth factor (VEGF) gene. Transitions C → A at nucleotide position −2578 relative to the translation start site, T → C at position −1455, G → A at position −1154, G → C at position −1001, and C → T at position −7 were observed. In addition, individuals with the A allele at position −2578 also had an insertion of 18 nucleotides, whereas CC homozygotes did not contain this insertion. We have described the frequency distribution of the polymorphic alleles in the population of healthy volunteers and are investigating the functional significance of the 18-nucleotide insertion and of the single-nucleotide polymorphisms on VEGF gene expression.     

Solute carrier family 11 member 1 genetic polymorphisms rs17235409 and rs3731865 associate with susceptibility to extremity post-traumatic osteomyelitis in a Chinese Han population

Genetic variations in the solute carrier family 11 member 1 (SLC11A1) gene have been implicated in developing inflammatory disorders. However, it is still unclear whether such polymorphisms contribute to the pathogenesis of post-traumatic osteomyelitis (PTOM). Therefore, this study investigated the roles of genetic variations of the SLC11A1 gene (rs17235409 and rs3731865) in PTOM development in a Chinese Han cohort. The SNaPshot method was used for genotyping 704 participants (336 patients and 368 controls) for rs17235409 and rs3731865. Outcomes revealed that rs17235409 increased the risk of PTOM occurrence by dominant (p = .037, odds ratio [OR] = 1.44) and heterozygous models (p = .035, OR = 1.45), implying AG genotype as a risk factor for PTOM development. In addition, patients with AG genotype had relatively higher levels of inflammatory biomarkers than those with AA and GG genotypes, especially for the white blood cell count and C-reactive protein. Despite no statistically significant differences achieved, rs3731865 may reduce the PTOM susceptibility, suggested by the results of dominant (p = .051, OR = 0.67) and heterozygous (p = .068, OR = 0.69) models. In short, rs17235409 confers an elevated chance of developing PTOM, with AG genotype as a risk factor. Whether rs3731865 involves in the pathogenesis of PTOM requires further investigations.     

Association of hepatocellular carcinoma risk with polymorphisms in tumour necrosis factor alpha gene in a Chinese Han population

Hepatocellular carcinoma (HCC) is the third leading cause of cancer‐related death worldwide. Studies have shown that the tumour necrosis factor alpha (TNF‐α) plays an important role in the development of HCC; however, the association between genetic variations of TNF‐α and HCC is not yet fully understood. To evaluate the correlation of TNF‐α polymorphisms with HCC, we randomly selected 327 HCC patients and 432 healthy controls, all these subjects reported Han nationality. Genotyping of four TNF‐α SNPs (rs1799724, rs1800629, rs1799964 and rs1800610) was performed using the matrix‐assisted laser desorption ionization‐time of flight mass spectrometry (MALDI‐TOF‐MS) method. Distributions of rs1799964 genotypes and rs1800610 alleles were found to be significantly different between cases and controls (p = .011, p = .001). The recessive model of rs1799964 significantly increased HCC risk (p = .0015), while the dominant and over‐dominant models of rs1800610 significantly reduced HCC risk (p = .0096, p = .014). Haplotype analysis of the four TNF‐α SNPs revealed that the TGTA haplotype was associated with a reduced HCC risk (p = .0033, OR = 0.53), while the TGTG haplotype was associated with an increased HCC risk (p = .0032, OR = 9.69). These findings indicated that specific TNF‐α polymorphisms may be associated with the susceptibility to HCC.     

MTTP variants and body mass index, waist circumference and serum cholesterol level: Association analyses in 7582 participants of the KORA study cohort

The microsomal triglyceride transfer protein (MTTP) is a key regulator in the assembly and secretion of chylomicrons and very low density lipoprotein (VLDL) in the intestine and in liver. Associations between MTTP variants and traits of the metabolic syndrome are carried out in relatively small cohorts and are not consistent.We analysed MTTP polymorphisms in 7582 participants of the KORA study cohort. Seven htSNPs covering a 52 kb region of the MTTP locus and two cSNPs (I128T, H297Q) were selected.A MTTP haplotype containing the minor allele of H297Q showed a significant decrease of −0.636 (95% CI: −1.226, −0.046; p = 0.035) BMI units in females but not in males. In comparison to homozygous H-carriers for the major allele of the MTTP H297Q polymorphism, homozygous Q297Q carriers showed a significant decrease in BMI of −0.425 BMI units (95% CI: −0.74, −0.12; p = 0.007), in waist circumference of −0.990 cm (95% CI: 1.74, −0.24; p = 0.01) and in total cholesterol of −0.039 mmol/l (95% CI: −0.07, 0; p = 0.03). Heterozygous Q-carriers displayed a reduction in BMI of −0.183 BMI unit (95% CI: −0.33, −0.04; p = 0.012), in waist circumference of −0.45 cm (95% CI: 0.8, −0.1; p = 0.01) and in total cholesterol of −0.103 mmol/l (95% CI: −0.18, −0.03; p = 0.01). Gender stratified statistics revealed a significant reduction of −0.657 BMI units (95% CI: −1.14, −0.18; p = 0.007), −1.437 cm waist circumference (95% CI: −2.55, −0.32; p = 0.01) and −0.052 mmol/l total cholesterol (95% CI: −0.1, −0.01; p = 0.03) for females homozygous for the Q297Q polymorphism. Females carrying the Q-allele showed a decrease of −0.259 BMI unit (95% CI: −0.48, −0.04; p = 0.023), −0.662 cm waist circumference (95% CI: −1.18, −0.14; p = 0.01) and −0.111 mmol/l total cholesterol (95% CI: −0.21, −0.01; p = 0.03).Our association analysis in a large population based study cohort provides evidence that the minor allele of the MTTP H297Q polymorphism is associated with lower BMI, waist circumference and total cholesterol in females but not in males.     

Vascular endothelial growth factor gene polymorphisms in spontaneously aborted fetuses

Citation Jeon YJ, Kim JH, Rah HC, Kim SY, Yoon TK, Choi DH, Cha SH, Shim SH, Kim NK. Vascular endothelial growth factor gene polymorphisms in spontaneously aborted fetuses. Am J Reprod Immunol 2011; 66: 544–553 Problems The VEGF?1154G>A polymorphism has been reported to be a genetic risk factor for recurrent spontaneous abortion in various studies; however, these studies have focused on genetic analyses of pregnant women rather than aborted fetuses. To evaluate and confirm the association between the VEGF?1154G>A polymorphism and spontaneous abortion, we focused on the relationship between four polymorphisms in the VEGF gene (?2578C>A, ?1154G>A, ?634G>C, and 936C>T) and spontaneously aborted fetuses (SAFs). Method of study The subjects included 118 SAFs at <20 weeks gestation and 380 normal controls consisting of children and adults. The polymorphisms were genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis. Results Spontaneously aborted fetuses exhibited significantly different frequencies of the ?2578CA+AA/?634CC and ?1154GA+AA/?634CC combined genotypes compared with control subjects. The frequency of the ?2578A/?1154A/?634C/936C haplotype was significantly higher in SAFs. Conclusions VEGF genes ?2578CA+AA/?634CC and ?1154GA+AA/?634CC in the fetus are possible risk factors for spontaneous abortion.     

Upstream transcription factor 1 (USF1) in risk of type 2 diabetes: association study in 2000 Dutch Caucasians

Type 2 diabetes shares substantial genetic and phenotypic overlap with familial combined hyperlipidemia. Upstream stimulatory factor 1 (USF1), a well-established susceptibility gene for familial combined hyperlipidemia, is postulated to be such a shared genetic determinant. We evaluated two established variants in familial combined hyperlipidemia (rs2073658 and rs3737787) for association with type 2 diabetes in two Dutch case-control samples (N = 2011). The first case-control sample comprised 501 subjects with type 2 diabetes from the Breda cohort and 920 healthy blood bank donors of Dutch Caucasian origin. The second case-control sample included 211 subjects with type 2 diabetes, and 379 normoglycemic controls. SNP rs2073658 and SNP rs3737787 were in perfect linkage disequilibrium. In the first case-control sample, prevalence of the major allele was higher in patients than in controls (75% versus 71%, OR = 1.25, p = 0.018). A similar effect-size and -direction was observed in the second case-control sample (76% versus 72%, OR = 1.22, p = 0.16). A combined analysis strengthened the evidence for association (OR = 1.23, p = 0.006). Notably, the increased risk for type 2 diabetes could be ascribed to the major allele, and its high frequency translated to a substantial population attributable risk of 14.5%.In conclusion, the major allele of rs2073658 in the USF1 gene is associated with a modestly increased risk to develop type 2 diabetes in Dutch Caucasians, with considerable impact at the population level.