OBJECTIVE: Asthma is a common, chronic, atopic respiratory disease that is on the rise among children and adults worldwide. Various environmental, genetic, and biological interactions contribute to the surge in susceptibility to this disease. Interleukin (IL) genes, particularly IL-4 and IL-13, have been linked to asthma pathogenesis. The present study aims to investigate the genetic aberrations, specifically single nucleotide polymorphisms (SNPs) of IL-4 and IL-13, and their association with childhood asthma and its severity.
METHODS: An unmatched hospital-based case-control study was conducted in a tertiary care hospital in Assam, India. The sample size was calculated to be 120 (60 cases and 60 controls) using the Epi Info software version 7.2 (Centers for Disease Control and Prevention, Atlanta, GA, USA), assuming a confidence interval of 95%, a power of the study at 80%, a ratio of control to cases as 1, a proportion of controls with exposure at 22%, and a proportion of cases with exposure at 46%. A total of 53 clinically diagnosed cases of childhood asthma in the age range of three to 12 years and 39 healthy controls free from respiratory diseases and having no history of asthma and/or allergy of the same age group attending a tertiary care hospital were included in the study. Children who never had asthma or allergies and who did not suffer from any upper or lower respiratory infections for the previous four weeks were considered controls. Prior informed consent and ethical clearance were obtained. Very seriously ill cases and controls were excluded from the study. The genetic investigation used polymerase chain reaction (PCR), followed by restriction fragment length polymorphism (RFLP), to discover SNPs in the IL-4 and IL-13 genes. Sequencing analysis was done for the cases with +2044 G>A of the IL-13 gene in relation to the severity of the disease. The difference in the proportions of specific SNPs between cases and controls was analyzed using the χ2 test (a p-value of <0.05 was considered significant).
RESULTS: Both the rs2070874 and rs2243250 polymorphisms of IL-4 showed no statistically significant associations. The mutation of the IL-13 gene in 1111C>T was higher among cases than controls. Both genotypic and allelic distributions of the +2044G>A polymorphism of the IL-13 gene revealed a significant association (p<0.05) with the severity of the disease.
CONCLUSIONS: Genetic aberrations in SNPs of IL-4 and IL-13 are prevalent among the pediatric patients of the study region. The SNP +2044G>A of IL-13 is instrumental in disease manifestation and severity among the pediatric population of the study region.

BACKGROUND: Surfactant protein D (SP-D) is a critical component of the innate immune system intrinsically linked to energy metabolism. However, the relationship of SP-D gene polymorphisms and gestational diabetes mellitus (GDM) remains unclear. In this study, we analyzed SP-D gene polymorphisms in GDM patients and nondiabetic controls and then determined the association of SP-D gene polymorphisms with GDM.
METHODS: We examined a common genetic polymorphism located in the SP-D coding region (rs721917, Met31Thr) in GDM patients (n = 147) and healthy pregnant controls (n = 97) by using a cleaved amplification polymorphism sequence-tagged sites (PCR-RFLP) technique. The level of SP-D protein in the serum of GDM patients and nondiabetic controls was determined by ELISA. The gene and allele frequencies of SP-D and their association with GDM as well as SP-D protein levels were analyzed and expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs).
RESULTS: We found that there was a significant association of the SP-D polymorphism (rs721917) with GDM. The SP-D (T/T) genotype was found in 11.6% and 21.6% of GDM patients and matched healthy controls, respectively (odds ratio, 0.473; 95% confidence interval, 0.235-0.952; P = 0.033), indicating that women with the (T/T) genotype had a lower prevalence of GDM (OR = 0.473). Women with the T/C genotype showed an increased risk of GDM (odds ratio, 2.440; 95% confidence interval, 1.162-5.123; P = 0.017). We did not observe corrections between glucose homeostasis markers and SP-D genotypes in women with GDM. Furthermore, serum SP-D levels were higher in GDM patients than in matched healthy controls.
CONCLUSIONS: This study found the first evidence that an SP-D gene polymorphism (rs721917) was associated with GDM, which may provide the basis for further study on how SP-D plays a regulatory role in GDM.

BACKGROUND: Previous studies examined the association of genetic variation in progesterone receptor (PR) gene (PGR) with ovarian cancer, possibly by altering the expression of PR-B isoform, but with mixed outcome.
OBJECTIVE: This study evaluated the association of PGR variants with ovarian cancer and associated features.
METHODS: This was a retrospective case-control study, which involved 82 women with ovarian cancer and 95 cancer-free women who served as controls. Genotyping was done by Taqman® SNP genotyping by qRT-PCR. The PGR variants tested were rs471767 (A > G), rs590688 (G > C), and rs10895068 (G > A). Stratification analyses were used for testing the correlation between the PGR variants with ovarian cancer susceptibility according to menstruation status, FIGO classification, pathological grade, and chemotherapy.
RESULTS: Significantly lower minor allele frequency (MAF) of rs10895068 was seen among ovarian cancer patients, thereby imparting disease protective nature to this variant. Significant association of rs10895068 genotypes with ovarian cancer was seen under the dominant model, but not other genetic models. FIGO classification correlated positively with rs471767 and rs10895068, while rs10895068 correlated positively with lymph node positivity. Three-locus haplotype analysis identified ACA and HCG haplotypes to be negatively associated with the risk of ovarian cancer.
CONCLUSIONS: This report confirms the contribution of PGR variants, specifically the rs10895068 (+331G/A) the etiology of ovarian cancer.

OBJECTIVE: To determine the associations between matrix metalloproteinase-2 (MMP-2, encoded by the MMP2 gene) 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke in a Chinese population.
METHODS: Patients with first and recurrent ischemic stroke were included. Serum MMP-2 was measured, and MMP2 1306C/T and 735C/T polymorphisms were detected. The associations between MMP2 1306C/T and 735C/T polymorphisms and first and recurrent ischemic stroke were analyzed.
RESULTS: Serum MMP-2 in patients with first and recurrent ischemic stroke was significantly higher compared with controls, and patients with recurrent ischemic stroke had higher MMP-2 than those with first ischemic stroke. The frequency of the CC genotype and C allele of MMP2 735C/T was highest in patients with recurrent ischemic stroke, followed by patients with first ischemic stroke, and controls. Conversely, the genotype and allele of MMP2 1306C/T did not significantly differ between groups. The CC genotype of MMP2 735C/T was independently associated with first and recurrent ischemic stroke (odds ratios = 1.45 and 1.64, respectively), as was the C allele of MMP2 735C/T (odds ratios = 1.68 and 1.77, respectively).
CONCLUSIONS: The CC genotype and C allele of MMP2 735C/T were associated with first and recurrent ischemic stroke in a Chinese population.

Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase (DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this double-blind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, SmaI restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2 (-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models (GG and CG), while 89.13% of healthy control subjects had dominant genetic models (CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls (P = 0.0002). The frequency of G alleles in the leukoaraiosis patients (71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower (χ2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes (Kruskal-Wallis H = 24.5955, P < 0.0001). In addition, the GG genotype of DDAH2 (-449 G/C) was more common in patients with leukoaraiosis. These findings suggest that the G allele of DDAH2 (-449 G/C) is a risk factor for leukoaraiosis morbidity and is correlated with high levels of asymmetric dimethylarginine. This study was approved by the Institutional Ethics Committee of The 2nd Affiliated Hospital of Harbin Medical University of China (approval No. KY2016-177) on July 28, 2016.

Autosomal short tandem repeats (asSTR) serve as genetic markers for discriminating individuals and have been extensively used for criminal investigations as well as the establishment of genetic relationships. Tri-allelic pattern usually occurs due to chromosomal duplication, trisomy, and chimerism during mitotic division, but a false tri-allelic pattern at the D7S820 locus was encountered in our laboratory during the analysis of a case exhibit. DNA isolation from exhibit for profiling was done as per manufacturer\'s protocol. This is the first report which observed false tri-allelic pattern (10, 11, 14.1 allele) on D7S820 locus by analysis with GlobalFiler™ PCR Amplification Kit in Indian population. Findings were re-confirmed using other available asSTR kits in the laboratory, viz., AmpFLSTR™ Identifiler™ Plus PCR Amplification Kit and PowerPlex® Fusion 6C System. Two alleles (10, 11) found at D7S820, apart from SE33 marker, showed homozygous condition, but one Off Marker (OMR) peak was observed before start of SE33 marker region with the analysis using PowerPlex® Fusion 6C System. As it has been confirmed that the OMR allele belongs to the SE33 locus, this could be possible because of the adjacent locations of the D7S820 and the SE33 in the GlobalFiler® PCR amplification kit. 14.1 allele appeared within the allelic window of D7S820. The false tri-allelic pattern was due to the overlapping of SE33 marker allele (1.2 repeat) with bin window of D7S820 Marker. This finding might create confusion for the establishment of genetic relationships. We, therefore, conclude that such uncommon observations with rare events should be carefully investigated and interpreted.

A central role for advanced glycation end products (AGE) and their receptor (RAGE) in the pathogenesis of multiple cancer types, including colorectal cancer (CRC) was reported. We investigated the association between CRC and rs2853807, rs77170610, rs184003, rs1035798, rs2070600, rs1800684, rs1800624, and rs1800625 RAGE gene (AGER) polymorphic variants. Study subjects comprised 293 CRC patients [186 colon cancer (CC) and 107 rectal cancer (RC)] patients), and 264 age-, gender-, BMI-, and ethnicity-matched controls. Minor allele frequency (MAF) of rs77170610 and rs1800625 were significantly lower, while MAF of rs1035798 was significantly higher in CRC patients compared to control subjects, which was associated with reduced and increased risk of CRC, respectively; MAF of the remaining variants was comparable between CRC patients and controls. Significant difference in the distribution of rs2853807 and rs77170610 genotypes was seen between CRC patients and controls, with both variants associated with decreased risk of CRC. Comparison of the distribution of minor allele-carrying genotypes in CC and RC patient subgroups revealed lack of significant difference in the distribution of these genotypes between the patient subgroups. In view of the lack of LD between rs2853807 and rs77170610 with other variants, six-locus (rs184003, rs1035798, rs2070600, rs1800684, rs1800624, rs1800625) haplotypes were constructed. Haplotype analysis did not identify any specific 6-locus AGER haplotype associated with CRC. In conclusion, AGER gene rs2853807 and rs77170610 variants rs77170610 are associated with altered risk of CRC in Tunisians, but with no discrimination between CC and RC types.

Secreted phosphoprotein-1 (SPP1) has been reported to be involved in the pathogenesis of breast cancer (BRC), but the influence of SPP1 single nucleotide polymorphisms on the BRC susceptibility has been rarely reported. In this study, we explored the association between rs11730582, rs2853750, and rs35893069 in the SPP1 gene and the BRC susceptibility. We used Snapshot assay to detect SPP1 single nucleotide polymorphisms in 471 BRC patients and 471 controls. The plasma SPP1 level was measured by ELISA. We found that the CC genotype and C allele of rs11730582 were associated with a significantly decreased BRC risk compared with the TT genotype and T allele, respectively [CC vs. TT: odds ratio (OR) = 0.59, 95% CI = 0.37-0.94, P = 0.026; C vs. T: OR = 0.79, 95% CI = 0.65-0.96, P = 0.022]. In addition, BRC patients and controls with the rs11730582 CC genotype had a lower plasma SPP1 level than did BRC patients and controls with TT genotype (P = 0.007 and P = 0.011, respectively). Moreover, the proportions of rs11730582 CC genotype and C allele were decreased in BRC patients with clinical stages I-III compared with those with clinical stage IV (P = 0.012 and P = 0.003, respectively). Besides, the C-G-T haplotype was associated with a significantly decreased BRC risk compared with the T-A-T haplotype (OR = 0.69, 95% CI = 0.52-0.93, P = 0.015). However, there was no significant association between rs2853750 or rs35893069 and the BRC risk. In summary, our study found the association between rs11730582 and the risk of BRC and suggested that rs11730582 may promote the occurrence and development of BRC by regulating SPP1 expression.

Insofar as altered NF-κB signaling stemming from the presence of specific genetic variants in NF-κB gene contribute to cancer pathogenesis, this study evaluated the association between NF-κB rs147574894/I552V, rs148626207/M860T rs3774937 and rs1598859 variants and breast cancer and associated features and complications. This was a retrospective case-control study, which involved 207 women with breast cancer, and 214 cancer-free women who served as controls. NF-κB genotyping was done by real-time PCR. Significantly higher rs3774937 minor allele frequencies (MAF), and lower rs147574894 MAF were seen among breast cancer patients, thereby imparting disease susceptibility and protective nature to these variants, respectively. Significant association of rs3774937 and rs147574894 genotypes with breast cancer was seen under the dominant model. Histological type and grade, molecular type, Her2 positivity and ER+/Her2- correlated positively, while distant metastasis negatively correlated with rs3774937. On the other hand, rs147574894 negatively correlated with histological type and grade, tumor size, Her2 positivity, molecular type, and ER+/Her2-, while rs148626207 correlated positively with histological grade, but negatively with distant metastasis and triple-negative status. Breast cancer-susceptible and -protective 4-locus haplotypes were also identified. This is the first report that addresses the contribution of NF-κB variants to the pathogenesis of breast cancer in Middle Eastern-North African population, and the first to document positive association of rs3774937 with breast cancer.

Several factors are involved in the periodontitis with host response through cytokines and as well as with influence of polymorphisms in cytokine genes, however the results remained contradictory. This study aimed at evaluating the rs1143634 polymorphism in interleukin-1B gene, a cytokine gene, and the risk of chronic periodontitis with conducting a meta-analysis focusing in ethnicity. A review in literature was performed in several databases to studies published before June 2017. Data extraction was performed by two calibrated investigators and the calculations of the meta-analysis were obtained through Review Manager version 5.2 statistical software with Odds Ratio (OR) calculation and Funnel plot (P < 0.05) to heterogeneity and the Comprehensive Meta-analysis version 3.3.070 to assessment publication bias by Egger\'s and Begg\'s tests. In overall, 54 case/control studies composed the meta-analysis. T allele was significantly associated with patients case (OR = 1.35, 95% CI: 1.24, 1.48, P < 0.00001) in the overall analysis. The stratified evaluation showed the rs1143634 polymorphism had significant association with disease in Caucasian, Asian and mixed population was excepted in African ethnicity (P > 0.05). No publication bias was found in allelic evaluation. This meta-analysis in 9376 participants with 54 case/control studies revealed the rs1143634 polymorphism was associated with elevated risk of chronic periodontitis in overall analysis as well as Caucasian and Asian ethnicities and Mixed population.