association of a rare variant of -93, -53 promoter gene polymorphisms of lipoprotein lipase gene with obesity and insulin resistance

Objectives: Obesity increases the risk of numerous chronic diseases. Obesity is classified clinically using body mass index [BMI], waist-to-hip ratio, and body fat percentage. The lipoprotein lipase [LPL] gene has been linked to lipoprotein metabolism and obesity. We performed a case-control study to determine the association between LPL gene polymorphisms and obesity-associated phenotypes such as insulin resistance [IR]

Methods: We examined the different LPL gene variants for association in 642 individuals segregated by BMI and IR. Genotyping of the LPL gene -93 and -53 promoter gene polymorphisms were analyzed using polymerase chain reaction-restriction fragment length polymorphism

Results: A substantial association was observed for -93 gene polymorphism of the LPL gene with obesity, while -53 promoter gene polymorphism showed association with IR

Conclusions: We found a significant association between -93 and -53 promoter gene polymorphisms of the LPL gene with obesity and associated phenotypes in the studied population

Common genetic variant of INSIG2 gene rs7566605 polymorphism is associated with severe obesity in North India

Background: Obesity is a very common disorder resulting from an imbalance between food intake and energy expenditure, and it has a substantial impact on the development of chronic diseases. The aim of this study was to examine the association of INSIG2 [rs7566605] gene polymorphism with obesity and obesity associated phenotypes in North Indian subjects

Methods: The variants were investigated for association in 642 obese and non-obese individuals. The genotyping of INSIG2 [rs7566605] single nucleotide polymorphism was analyzed by the TaqMan allelic discrimination protocol

Results: A significant association was observed for INSIG2 [rs7566605] single nucleotide polymorphism with obesity and obesity-related phenotypes. Furthermore, a significant relationship was found between the rs7566605 and insulin, homeostasis model of assessment-insulin resistance, the percentage of body fat, fat mass, leptin, and adiponectin

Conclusion: The present study observed significant association between INSIG2 [rs7566605] single nucleotide polymorphism and obesity, as well as obesity associated phenotypes in North Indian population

Association of FTO rs9939609 SNP with obesity and obesity- associated phenotypes in a north Indian population

Objectives: Obesity is a common disorder that has a significant impact on morbidity and mortality. Twin and adoption studies support the genetic influence on variation of obesity, and the estimates of the heritability of body mass index [BMI] is significantly high [30 to 70%]. Variants in the fat mass and obesity-associated [FTO] gene have been associated with obesity and obesity-related phenotypes in different populations. The aim of this study was to examine the association of FTO rs9939609 with obesity and related phenotypes in North Indian subjects

Methods: Gene variants were investigated for association with obesity in 309 obese and 333 non-obese patients. Genotyping of the FTO rs9939609 single nucleotide polymorphism [SNP] was analyzed using Restriction Fragment Length Polymorphism Analysis of PCR-Amplified Fragments. We also measured participants fasting glucose and insulin levels, lipid profile, percentage body fat, fat mass and fat free mass

Results: Waist to hip ratio, systolic blood pressure, diastolic blood pressure, percentage body fat, fat mass, insulin concentration, and homeostasis model assessment index [HOMA-Index] showed a significant difference between the study groups. Significant associations were found for FTO rs9939609 SNP with obesity and obesity-related phenotypes. The significant associations were observed between the rs9939609 SNP and blood pressure, fat mass, insulin, and HOMA-index under a different model. Conclusion: This study presents significant association between FTO rs9939609 and obesity defined by BMI and also established the strong association with several measures of obesity in North Indian population

Achalasia Is Associated With eNOS4a4a, iNOS22GA, and nNOS29TT Genotypes: A Case-control Study

BACKGROUND/AIMS: Achalasia is known to result from degeneration of inhibitory neurons, which are mostly nitrinergic. Characteristic features of achalasia include incomplete lower esophageal sphincter (LES) relaxation and esophageal aperistalsis. Nitric oxide (NO), produced by NO synthase (NOS), plays an important role in peristalsis and LES relaxation. Therefore, we evaluated genetic polymorphisms of NOS gene isoforms (endothelial NOS [eNOS], inducible NOS [iNOS], and neuronal NOS [nNOS]) in patients with achalasia and healthy subjects (HS). METHODS: Consecutive patients with achalasia (diagnosed using esophageal manometry) and HS were genotyped for 27-base pair (bp) eNOS variable number of tandem repeats (VNTR), iNOS22G/A (rs1060826), nNOS C/T (rs2682826) polymorphisms by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism (RFLP), respectively. RESULTS: Among 183 patients (118 [64.5%] male, age 39.5 +/- 13.0 years) with achalasia and 366 HS (254 [69.4%] male, age 40.8 +/- 11.0 years), eNOS4a4a genotype of 27-bp VNTR was more common among achalasia than HS (20 [10.9%] vs 13 [3.6%]; P < 0.001; OR, 3.72; 95% CI, 1.8-7.7). Patients with achalasia had iNOS22GA genotypes more often than HS (95 [51.9%] vs 93 [25.4%]; P < 0.001; OR, 3.0; 95% CI, 2.1-4.4). Frequency of genotypes GA + AA was higher in patients than HS (97 [53%] vs 107 [29.2%]; P < 0.001; OR, 2.7; 95% CI, 1.8-3.9). Also, nNOS29TT variant genotype in rs2682826 was more common among patients compared to HS (14 [7.7%] vs 6 [1.6%]; P < 0.001; OR, 5.91; 95% CI, 2.2-15.8). CONCLUSIONS: Achalasia is associated with eNOS4a4a, iNOS22GA, and nNOS29TT genotypes. This may suggest that polymorphisms of eNOS, iNOS, and nNOS genes are risk factors for achalasia.

Evaluation of MC4R [rs17782313, rs17700633], AGRP [rs3412352] and POMC [rs1042571] polymorphisms with obesity in Northern India

Genetic variants of the melanocortin-4 receptor gene [MC4R], agouti related protein [AGRP] and proopiomelanocortin [POMC] are reported to be associated with obesity. Therefore, the aim of this study is to examine MC4R rs17782313, MC4R rs17700633, AGRP rs3412352 and POMCrs1042571 for any association with obesity in North Indian subjects. The variants were investigated for association in 300 individuals with BMI >/= 30 kg/m2 and 300 healthy non-obese individuals BMI <30 kg/m[2]. The genotyping were analyzed by Taqman probes. The statistical analysis was performed by the SPSS software, ver.19 and p /= 30 kg/m2] in North Indian subjects. This study provides the report about the significant association of MC4R [rs17782313] and POMC [rs1042571] with morbid obesity [BMI >/= 30 kg/m2], but MC4R [rs17700633] and AGRP [rs34123523] did not show any association with obesity in the studied North Indian population.

Association of cytokine gene polymorphisms in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease [COPD] is a major health problem. The disease is driven by abnormal inflammatory reactions in response to inhaled particles and fumes. Therefore, inflammatory mediators are postulated to be of distinct importance. Keeping in view of the above facts; we investigate the role of polymorphisms of cytokine genes in the genetic predisposition of COPD. In this present case-control study, the allele and genotype distributions of IL1B, IL1RN, TNF-alpha, and IL4 were studied in COPD patients [N=204] and healthy individuals [N=208]. Genomic DNA was obtained by whole blood and genotyping was carried out by a polymerase chain reaction [PCR] based Restriction Fragment Length Polymorphism technique. Genotype IL1RN*2/IL1RN*2 was identified as protective for male COPD, its frequency being 8.7% in COPD patients and 14.6% in healthy subjects [p=0.017; OR=0.53], but IL1RN*1/IL1RN*2 turned out to be a risk factor for females COPD. No significant differences were found between the groups of COPD patients and healthy subjects concerning the genotype frequencies of the polymorphisms T [-511] C of IL1B and 70bp VNTR of IL-4. Genotype GA of the TNF-alpha polymorphism G [-308] A was more common in the COPD patients than in the controls [20.5% vs.14.4%; p=0.107], and allele A was significantly associated with COPD patients [p=0.023; OR=0.65]. IL-1RN *2 allele appears to be significantly associated with the COPD female patients and TNF-alpha-308A allele is a risk factor for the development of COPD

Genotype-Phenotype correlation of SMN locus genes in spinal muscular atrophy patients from India

Spinal muscular atrophy has been classified into four groups based on the age of onset and clinical severity of the disease. Homozygous deletion in SMN1 gene causes the disease but the clinical severity may be modified by copy number of homologous gene SMN2 as well as the extent of deletion at SMN locus. In the view of scarcity of genotype and phenotype correlation data from India, this study has been undertaken to determine that correlation in SMA patients by using the SMN and NAIP genes and two polymorphic markers C212 and C272 located in this region. Two to four alleles of the markers C212 and C272 were observed in normal individuals. However, majority of Type I patients showed only one allele from both markers whereas in Type II and III patients, 2-3 alleles were observed. The SMN2 copy number in our type III patients showed that patients carry 3-5 copies of SMN2 gene. Our results suggest that extent of deletions encompassing H4F5, SMN1, NAIP and copy number of SMN2 gene can modify the SMA phenotype, thus accounting for the different clinical subtypes of the disease.

Microsatellite instability and its correlation with clinicopathological features in a series of thyroid tumors prevalent in iodine deficient areas

Thyroid tumors display diverse spectrum of histopathological groups with geographic variation in its prevalence. Influence of iodine deficiency (a major causative factor) in its etiology, prevalence, or aggressiveness is debatable which reflects the existence of various genetic events in pathogenesis. The present study was undertaken to study the role of Microsatellite instability (MSI) or LOH (loss of heterozygosity), an indicator of defective mismatch repair system as a genetic change and to explore it as a prognostic marker in thyroid tumors. Tumor tissues from total thyroidectomy surgical specimens and blood (matched control) of 36 patients from iodine deficient areas (10 benign; 26 malignant) were obtained after their consent. Urinary iodine analysis was done by alkali ash method for which 10 ml of urine was collected from 18 patients before surgery. Genomic DNA, isolated from tumor tissue and blood was amplified by polymerase chain reaction (PCR) using mono and dinucleotide markers - BAT-26, BAT-40, TGF(RII, IGFIIR, hMSH3, BAX, D2S123, D9S283, D9S851 and D18S58. PCR products were analysed on 8% denaturing polyacrylamide gel followed by autoradiography. Of total, 66.6% of tumors [70% (7/10) benign and 65.4% malignant cases (17/26)] showed MSI/LOH. Strong association of MSI/LOH with low iodine (P=0.01) and with AMES risk groups i.e. age (P=0.02), tumor size (P=0.04) and metastases (P=0.002) in thyroid tumors was observed. This may help in predicting the biological behaviour and strengthening the hypothesis that iodine deficiency has influence on MSI in thyroid tumors. Our results further substantiate the risk group classification and help in deciding the treatment modality in particular patient.

De novo mutations in sporadic deletional Duchenne muscular dystrophy (DMD) cases

Dinucleotide repeat polymorphism based genetic analysis is a powerful approach to gain insight into rare genetic events like germline mosaicism and de novo mutations. The loss of heterozygosity of polymorphic dinucleotide loci at "deletional hotspot" of dystrophin gene can provide direct evidence of carrier status in female relatives of affected DMD patients with overlapped exonic deletions. We have used 4 STR loci of the central deletional hotspot of the dystrophin gene for genetic analysis in sporadic unrelated DMD families. Twenty-nine mothers of sporadic deletional cases were analysed and their carrier status was determined. Eighteen of them showed heterozygosity in the deleted loci suggesting the occurrence of de novo mutations. In 9 cases, the carrier status was indeterminate while 2 showed germline mosaicism. Our observations reiterated the importance of STR analysis in determining the status of mothers of sporadic deletional DMD cases in order to provide proper genetic counselling.