The −14010*C variant associated with lactase persistence is located between an Oct-1 and HNF1α binding site and increases lactase promoter activity

In most people worldwide intestinal lactase expression declines in childhood. In many others, particularly in Europeans, lactase expression persists into adult life. The lactase persistence phenotype is in Europe associated with the −13910*T single nucleotide variant located 13,910 bp upstream the lactase gene in an enhancer region that affects lactase promoter activity. This variant falls in an Oct-1 binding site and shows greater Oct-1 binding than the ancestral variant and increases enhancer activity. Several other variants have been identified very close to the −13910 position, which are associated with lactase persistence in the Middle East and Africa. One of them, the −14010*C, is associated with lactase persistence in Africa. Here we show by deletion analysis that the −14010 position is located in a 144 bp region that reduces the enhancer activity. In transfections the −14010*C allele shows a stronger enhancer effect than the ancestral −14010*G allele. Binding sites for Oct-1 and HNF1α surrounding the −14010 position were identified by gel shift assays, which indicated that −14010*C has greater binding affinity to Oct-1 than −14010*G.     

MCP-1 −2518 A/G functional polymorphism is associated with increased susceptibility to active pulmonary tuberculosis in Tunisian patients

Monocyte chemoattractant protein-1 (MCP-1) plays crucial role in protective immunity against Mycobacterium tuberculosis (MT). In this study, we examined whether single nucleotide polymorphism (SNP) −2518 A/G (rs 1024611) of MCP-1 affect the susceptibility to active tuberculosis (TB) in Tunisian populations. Genomic DNA from patients with active TB (168 cases of pulmonary TB and 55 cases of extrapulmonary TB) and ethnically controls (150 cases) was genotyped for the MCP-1 −2518 A/G SNP by polymerase chain reaction fragment length polymorphism (PCR-RFLP). We observed that −2518 G allele and GG genotype (high MCP-1 producer) frequencies were significantly more elevated in active pulmonary TB group in comparison to control group [34 vs. 22%; P = 0.0007; 15 vs. 5%, P corrected for the number of genotypes (Pc) = 0.015; respectively]. Additionally, they were associated with increased risk development of this clinical form of TB [odds ratio (OR) = 1.83, 95% confidence intervals (CI) = 1.26–2.66; OR = 3.1, 95% CI = 1.28–7.76; respectively]. However, wild type allele −2518 A and AA genotype were over-represented in control group (78 and 62%) and seem to be protective factors against TB. Moreover, −2518 AA genotype was more frequent in control group and was associated with resistance against development of active pulmonary TB (OR = 0.56, 95% CI = 0.35–0.89, Pc = 0.03). Our findings confirm the key role of −2518 A/G SNP of MCP-1 and support its association with resistance/susceptibility to the development of active pulmonary TB in the Tunisian population.     

G allele of the −930A>G polymorphism of the CYBA gene is associated with insulin resistance in obese subjects

It has been shown that NADPH oxidase plays a role in oxidative stress which has been involved in the development of metabolic syndrome. The ?930A/G polymorphism of the CYBA gene (that codes p22phox, a major component of the NADPH oxidase) has been associated with human hypertension and with a reduction in NADPH oxidase activity. In this work, we have examined the influence of the ?930A/G polymorphism on obesity risk and insulin resistance in a case-control study of Spanish subjects (n=313). In the obese group (n=159), there was a statistically significant association between the GG genotype of the ?930A/G polymorphism of the CYBA gene and fasting insulin levels and HOMA index. This outcome agrees with previous findings concerning functional analyses of this polymorphism and reinforces the hypothesis that insulin resistance is associated with oxidative stress. In conclusion, a protective effect in carriers of the ?930A/G, polymorphism of the p22phox gene against insulin resistance in a population of Spanish obese adults has been found.     

The human lactase persistence-associated SNP ?13910*T enables in vivo functional persistence of lactase promoter–reporter transgene expression

Lactase is the intestinal enzyme responsible for digestion of the milk sugar lactose. Lactase gene expression declines dramatically upon weaning in mammals and during early childhood in humans (lactase nonpersistence). In various ethnic groups, however, lactase persists in high levels throughout adulthood (lactase persistence). Genetic association studies have identified that lactase persistence in northern Europeans is strongly associated with a single nucleotide polymorphism (SNP) located 14 kb upstream of the lactase gene: -13910*C/T. To determine whether the -13910*T SNP can function in vivo to mediate lactase persistence, we generated transgenic mice harboring human DNA fragments with the -13910*T SNP or the ancestral -13910*C SNP cloned upstream of a 2-kb rat lactase gene promoter in a luciferase reporter construct. We previously reported that the 2-kb rat lactase promoter directs a post-weaning decline of luciferase transgene expression similar to that of the endogenous lactase gene. In the present study, the post-weaning decline directed by the rat lactase promoter is impeded by addition of the -13910*T SNP human DNA fragment, but not by addition of the -13910*C ancestral SNP fragment. Persistence of transgene expression associated with the -13910*T SNP represents the first in vivo data in support of a functional role for the -13910*T SNP in mediating the human lactase persistence phenotype.     

Is A163G polymorphism in the osteoprotegerin gene associated with heel velocity of sound in postmenopausal women?

Osteoprotegerin (OPG) plays an important inhibitory role in osteoclastogenesis. Polymorphisms in the OPG gene recently have been associated with various bone phenotypes including fractures. The aim of the present study was to investigate the association between three informative OPG polymorphisms and quantitative ultrasound variables of the heel. In a cohort of 165 perimenopausal women polymorphisms in the OPG promoter (A163G, T245G) and in exon 1 (G1181C) were assessed by PCR-RFLP analysis. The distribution of the investigated genotypes was similar to other Caucasian women (A163G-AA 68 %, AG 30 %, GG 2 %, T245G-TT 84.4 %, TG 15 %, GG 0.6 %, G1181C- GG 22 %, CG 55 %, CC 23 %). After adjustment for body mass index and years since menopause, in a subgroup of 87 postmenopausal subjects, calcaneal velocity of sound (VOS, m/s) was significantly associated with A163G polymorphism (p=0.0102, ANCOVA). Women with the presence of G allele (AG+GG genotypes) had significantly lower VOS than women with AA genotype. Neither T245G nor G1181C were associated with calcaneal ultrasound indices. In conclusion, A163G polymorphism was significantly associated with VOS at the heel in a limited cohort of postmenopausal women. The present study replicated in part the previous findings about OPG gene variations and peripheral bone mass in Caucasian women.     

DNA typing forHLA-DPB1*02 and−DPB1*04 in multiple sclerosis and juvenile rheumatoid arthritis

DP gene typing using in vitro DNA amplification combined with sequence-specific oligonucleotide probes (SSOP) has recently been reported. The amplification step may be specific for theHLA-DPB locus, or it may be specific for one or a group ofHLA-DPB alleles, thus increasing the discriminatory power of the system. We report the combined use of group-specific DNA in vitro amplification followed by SSOP in typing forDPB1*02 andDPB1*04 variants. The method was used to type for these variants in 96 randomly selected, healthy Danes, in 37 patients with pauciarticular juvenile rheumatoid arthritis (PJRA); and in 38 patients with multiple sclerosis (MS). Increased frequencies of the cellularly defined HLA-DPw2 in PJRA and of HLA-DPw4 in MS have previously been reported. In the patient groups, the frequencies of theDPB1*02 andDPB1*04 variants did not differ significantly from those expected based on the cellularly defined HLA-DP types of the patients and the frequencies of theDPB1*02 andDPB1*04 variants among healthy Danes.     

Mortality in adult intensive care patients with severe systemic inflammatory response syndromes is strongly associated with the hypo-immune TNF −238A polymorphism

The systemic inflammatory response syndrome (SIRS) is associated with activation of innate immunity. We studied the association between mortality and measures of disease severity in the intensive care unit (ICU) and functional polymorphisms in genes coding for Toll-like receptor 4 (TLR4), macrophage migratory inhibitory factor (MIF), tumour necrosis factor (TNF) and lymphotoxin-alpha (LTA). Two hundred thirty-three patients with severe SIRS were recruited from one general adult ICU in a tertiary centre in the UK. DNA from patients underwent genotyping by 5′ nuclease assay. Genotype was compared to phenotype. Primary outcome was mortality in ICU. Minor allele frequencies were TLR4 +896G 7%, MIF 173C 16%, TNF ?238A 10% and LTA +252G 34%. The frequency of the hypoimmune minor allele TNF ?238A was significantly higher in patients who died in ICU compared to those who survived (p?=?0.0063) as was the frequency of the two haplotypes LTA +252G, TNF ?1031T, TNF ?308G, TNF ?238A and LTA +252G, TNF?1031T, TNF?308A and TNF?238A (p?=?0.0120 and 0.0098, respectively). These findings re-enforce the view that a balanced inflammatory/anti-inflammatory response is the most important determinant of outcome in sepsis. Genotypes that either favour inflammation or its counter-regulatory anti-inflammatory response are likely to influence mortality and morbidity.     

Gene polymorphism of vascular endothelial growth factor −1154 G>A is associated with hypertensive nephropathy in a Hispanic population

The aim of this study was to determine the association between hypertensive nephropathy and gene polymorphisms of vascular endothelial growth factor (VEGF) in a self-reported Hispanic patient group. A total of 155 Hispanic living kidney donors as controls and a total of 86 Hispanic kidney transplant patients, whose renal failure was attributed to hypertensive nephropathy after ruling out diabetes mellitus or other causes, were genotyped for four different single nucleotide polymorphisms of VEGF: −2578 C>A (rs699947), −1154 G>A (rs1570360), −460 C>T (rs833061), and +936 C>T (rs3025039). The homozygous mutant type (AA) of VEGF −1154 G>A (rs1570360) was found with significantly higher frequency in the hypertensive nephropathy patients than in controls. On the other hand, homozygous wild type (GG) was found less frequently in the hypertensive nephropathy patient group than in the control group. Linkage disequilibrium (LD) analyses revealed a high degree of LD among VEGF −2578 C>A (rs699947), VEGF −1154 G>A (rs1570360), and VEGF −460 C>T (rs833061). The haplotype analysis revealed that two haplotypes, CGTC and CATC (in the order of VEGF −2578 C>A (rs699947), −1154 G>A (1570360), −460 C>T (rs833061), and +936 C>T (3025039)), were significantly associated with hypertensive nephropathy in Hispanic patients. Hence, the −1154 G>A polymorphism (rs1570360) and two haplotypes (CGTC and CATC) of VEGF appear to be associated with hypertensive nephropathy in Hispanic patients who developed end-stage renal disease requiring kidney transplant.     

No association of monocyte chemoattractant protein-1 −2518 A/G polymorphism with the risk of primary glomerulonephritis in the Polish population

Various studies have indicated that chemokines such as monocyte chemotactic protein-1 (MCP-1) play an important role in the pathogenesis of primary glomerulonephritis (GN) and other glomerular diseases. Moreover, patients with primary GN display aberrant galactosylation of the O-linked carbohydrate moieties of IgA. Therefore, we analysed the distribution of the functional MCP-1 −2518 A > G (rs 1024611) and 1 beta 1,3-galactosyltransferase (C1GalT1) 1365 A > G (rs1047763) polymorphic variants in patients with primary GN (n = 144) and controls (n = 437) in a sample of the Polish population. We did not find a significant difference in the prevalence of the MCP-1 −2518 A > G and C1GalT1 1365 A > G polymorphisms in patients with primary GN and healthy individuals. Odds Ratio (OR) for GN patients with the MCP-1 −2518 GG genotype was 0.869 (95% CI = 0.410–1.840, P = 0.7130), and OR of the −2518 GG and −2518AG genotypes was 1.004 (95% CI = 0.689–1.464, P = 0.9836). OR for C1GalT1 1365AA genotype was 0.484 (95% CI = 0.181–1.293, P = 0.1402) and OR of the 1365AA and 1365AG genotypes was 0.839 (95% CI = 0.573–1.228, P = 0.3651). We also did not observe a difference in the distribution of alleles between patients and controls. The MCP-1 −2518 G allelic OR was 0.976 (95% CI = 0.725–1.314, P = 0.8744). The OR for the C1GalT1 1365A allele was 0.816 (95% CI = 0.596–1.118, P = 0.205). Moreover, there was no significant association between the MCP-1 −2518 A > G and C1GalT1 1365 A > G genotypes with different morphological types of primary GN or clinical manifestations. Our observations indicate that the MCP-1 −2518 A > G and C1GalT1 1365 A > G polymorphisms might not be a risk factor in the incidence of primary GN in the Polish population.     

PRND 3′UTR polymorphism may be associated with behavioral disturbances in Alzheimer disease

The etiology of behavioral and psychological symptoms of dementia (BPSD) is complex, including putative biological, psychological, social and environmental factors. Recent years have witnessed accumulation of data on the association between genetic factors and behavioral abnormalities in Alzheimer disease (AD). In this research paper, our aim was to evaluate the association between the APOE, CYP46, PRNP and PRND genes and the profile of neuropsychiatric symptoms in Polish subjects with AD and mild cognitive impairment (MCI). We studied 99 patients with AD and 48 subjects with MCI. The presence and profile of BPSD were evaluated at baseline and prospectively with the Neuropsychiatric Inventory (NPI). Patients were dichotomized into those having ever experienced a particular symptom and those who did not over the whole disease period. Genotyping was performed using previously described standard protocols. The prevalence of comorbid behavioral symptoms and the overall level of behavioral burden were significantly greater in AD compared with the MCI group. In AD patients, carrier status of the T allele of the 3′UTR (untranslated region) PRND polymorphism was associated with an increased cumulative behavioral load and an elevated risk for delusions, anxiety, agitation/aggression, apathy and irritability/emotional ability. Among MCI subjects, APOE ε4 carriers demonstrated a reduced risk for nighttime behavior change. No other statistically significant genotype-phenotype correlations were observed, including the APOE, CYP46 and PRNP genes. A precise estimation of the exact significance of particular polymorphisms in BPSD etiology requires future studies on large populations.Key words: Alzheimer disease, mild cognitive impairment, behavioral symptoms, APOE, CYP46, PRNP, PRND, polymorphisms     

The Ku70 ?1310C/G promoter polymorphism is associated with breast cancer susceptibility in Chinese Han population

Ku70 plays an important role in the DSBR (DNA double-strand breaks repair) and maintenance of genomic integrity. Genetic variations within human Ku70 have been demonstrated to be associated with increased risk of several types of cancers. In this hospital-based case–control study, we aimed to investigate whether a single nucleotide polymorphism (SNP) in the promoter region (rs2267437) of Ku70 gene is associated with susceptibility to breast cancer in Chinese Han population. A total of 293 patients with breast cancer and 301 age-matched healthy controls were enrolled in this study. The Ku70 −1310C/G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) analysis. A significant difference in genotype distribution and allele frequency was observed between patients and controls. The CG or GG carries were at higher risk of breast cancer compared with the CC homozygotes (OR = 1.43, 95% CI = 1.02–2.00, P = 0.038 and OR = 3.53, 95% CI = 1.60–7.80, P = 0.002, respectively). Further stratification analysis revealed that G allele was associated with an increased risk of breast cancer among premenopausal women (OR = 1.68, 95% CI = 1.21–2.33, P = 0.002), but not in postmenopausal women (OR = 1.33, 5% CI = 0.85–2.10, P = 0.216). Our study suggests that the Ku70 −1310C/G promoter polymorphism may be a susceptibility factor for breast cancer in Chinese Han population.     

DIXDC1 co-localizes and interacts with γ-tubulin in HEK293 cells

DIXDC1 is a Dishevelled-Axin (DIX) domain-containing protein involved in neural development and Wnt signaling pathway. Besides the DIX domain, DIXDC1 also contains a coiled-coil domain (MTH domain), which is a common feature of centrosomal proteins. We have demonstrated that exogenously expressed GFP-tag fused DIXDC1 co-localize with γ-tubulin both at interphase and mitotic phase in HEK293 cells. By immunostaining with anti-DIXDC1 and anti-γ-tubulin antibody, endogenous DIXDC1 was also co-localized with γ-tubulin at the centrosomes in HEK293 cells. We confirmed this interaction of DIXDC1 with γ-tubulin by co-immunoprecipitation. The findings suggest that DIXDC1 might play an important role in chromosome segregation and cell cycle regulation.     

A single nucleotide polymorphism in NF-κB inducing kinase is associated with mortality in septic shock

We tested the hypothesis that single nucleotide polymorphisms (SNPs) within genes of the NF-κB pathway are associated with altered clinical outcome of septic shock patients. We genotyped 59 SNPs in the NF-κB pathway in a discovery cohort of septic shock patients (St. Paul's Hospital [SPH], N = 589), which identified the C allele of rs7222094 T/C within MAP3K14 (NF-κB inducing kinase; NIK) associated with increased 28-d mortality (uncorrected p = 0.00024, Bonferroni corrected p = 0.014). This result was replicated in a second cohort of septic shock patients (Vasopressin and Septic Shock Trial [VASST; N = 616]) in which the CC genotype of rs7222094 was associated with increased 28-d mortality (Cox regression: SPH cohort hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.12-1.64; p = 0.002 Caucasian only; and VASST cohort HR, 1.24; 95% CI, 1.00-1.52; p = 0.048 Caucasian only). Patients having the CC genotype of rs7222094 in SPH experienced more renal and hematological dysfunction (p = 0.003 and p = 0.011), while patients of the VASST cohort with the rs7222094 CC genotype showed the same trend toward more renal dysfunction. In lymphoblastoid cell lines, we found the rs7222094 genotype most strongly associated with mRNA expression of CXCL10, a chemokine regulated by NF-κB. Accordingly, we measured CXCL10 protein levels and found that the CC genotype of rs7222094 was associated with significantly lower levels than those of the TT genotype in lymphoblastoid cell lines (p < 0.05) and in septic shock patients (p = 0.017). This suggests that the CC genotype of NIK rs7222094 is associated with increased mortality and organ dysfunction in septic shock patients, perhaps due to altered regulation of NF-κB pathway genes, including CXCL10.     

Cyclin D1 G870A polymorphism is associated with an increased risk of hepatocellular carcinoma in the Turkish population: Case–control study

Background: A common G to A polymorphism (G870A) in the splice donor region of exon 4 of cyclin D1 (CCND1) gene generates two mRNAs (cyclin D1a and D1b) through an alternative splicing at the site of this polymorphism. Cyclin D1a and b proteins differ in their COOH-terminus, a region involved in protein degradation. We examined the association between this CCDN1 genotype and the susceptibility to hepatocellular carcinoma (HCC) in a Turkish population. Methods: The genotype frequency of this polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay. Hospital-based case–control study was designed consisting of 160 diagnosis subjects with hepatocellular carcinoma and 160 cancer-free control subjects matched on age, gender, smoking and alcohol status. Results: The allele frequencies of case subjects (A, 0.55; G, 0.45) were significantly different from those of control subjects (A, 0.42; G, 0.58) (p = 0.002). The odds ratios (ORs) for the CCND1 870 GA and AA genotypes when compared with the GG genotypes were 1.39 (95% confidence interval [CI] 0.82–2.36, p = 0.22) and 2.52 (95% CI 1.38–4.62, p = 0.003) respectively. The presence of at least one CCND1 870A allele was associated with increased risk for HCC (OR, 1.73; 95% CI, 1.06–2.82, p = 0.03). When combining the GG and GA genotypes as a reference genotype, we found that the OR for the AA genotype was 2.06 (95% CI 1.24–3.44, p = 0.006). Conclusion: Our results suggest that the CCND1 G870A single nucleotide polymorphism is associated with an increased risk of HCC in our Turkish population.     

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.     

Plasma visfatin,associated with a genetic polymorphism −1535C > T,is correlated with C-reactive protein in Chinese Han patients with traumatic brain injury

Visfatin is a newly identified pro-inflammatory adipokine and a genetic polymorphism −1535 C > T located in the visfatin gene promoter has been suggested to be associated with the regulation of visfatin expression in some inflammatory illness. However, there were some conflicting results regarding whether this variant is functional or not. This study aimed to examine the relations of the −1535 C > T single nucleotide polymorphism (SNP) of visfatin gene to the plasma visfatin and C-reactive protein concentrations in traumatic brain injury (TBI). 318 Chinese Han patients with TBI were recruited in this study. Plasma visfatin and C-reactive protein levels were significantly different between the genotypes in the SNP-1535 C > T even after adjustment for age, sex and body mass index. The genotype C–C had the highest plasma visfatin and C-reactive protein concentrations. The plasma visfatin and C-reactive protein concentrations between the variant genotypes C–T and T–T did not differ significantly. Plasma visfatin level was significantly associated with plasma C-reactive protein level using multivariate linear regression. Thus, the SNP-1535 C > T of visfatin gene seemed to be potentially involved in the inflammatory component of TBI through a decreased production of visfatin.     

The polymorphism of CLOCK gene rs4864548 A>G is associated with susceptibility of Alzheimer’s disease in Chinese population

The aim of this study was to investigate the correlation between polymorphism of circadian locomotor output cycle kaput (CLOCK) gene rs4864548 A/G and susceptibility of Alzheimer’s disease (AD). A total of 296 unrelated AD patients and 423 control subjects were enrolled in the case-control study. Genotypes of apolipoprotein E (APOE) and CLOCK gene rs4864548 A/G were determined by a Polymerase Chain Reaction (PCR) restriction fragment length polymorphism detection method. Our results showed that in the whole sample or APOE ε 4 non-carriers, prevalence of A carriers in CLOCK gene rs4864548 A/G in AD patients was remarkably higher than that in control subjects (in the whole sample: χ² = 47.614, p < 0.0001; in APOE ε 4 non-carriers: χ² = 22.493, p < 0.0001). However, among APOE ε 4 carriers, the difference in the prevalence of A carriers in CLOCK gene rs4864548 A/G between AD patients and controls was no statistically significant (χ² = 0.669, p = 0.379). These findings demonstrate that A carriers in CLOCK gene rs 4864548 A/G were closely related to a high susceptibility of AD among APOE ε 4 non-carriers while the functional polymorphism of CLOCK gene rs4864548 A/G was not associated with the susceptibility of AD among APOE ε 4 carriers.     

Protective role of IL-18 −137G/C polymorphism in a North Indian population with asthma: A pilot study

BackgroundIL-18, a pleiotropic, pro-inflammatory cytokine that plays a major role in innate as well as acquired immunity, has been implicated in asthma etiology and this is the first study investigating the role of IL-18 ?137G/C (rs 187238) promoter polymorphism in asthma pathogenesis in a North Indian population.MethodsA pilot study was conducted with a total of 824 subjects, out of which 410 were asthma patients including 323 patients suffering from allergic rhinitis and 414 healthy controls from regions of North India. Tetra-Primer Amplification Refractory Mutation System Polymerase Chain Reaction (Tetra-Primer ARMS PCR) was used for genotyping the IL-18 ?137G/C polymorphism.ResultsWhile the homozygous wild (GG) genotype was equally prevalent in asthma patients as well as control subjects (70.0%), the homozygous mutant (CC) genotype was more prevalent among the controls (8.0%) than in asthma patients (3.4%), which yielded a significant protection or decreased risk towards asthma. Statistical analysis revealed Odds Ratio (OR) = 0.43 (95% CI = 0.21–0.85), Chi² (χ²) = 6.93 and p-value = 0.008 (p < 0.005). Moreover, a few asthma phenotypic traits also revealed significant protective associations with the polymorphism.ConclusionsThe IL-18 ?137G/C polymorphism confers a significant protection from asthma in the studied North Indian population. This is the first study to report the protective association of the polymorphism with the disease.