A multianalytical approach to evaluate the association of 55 SNPs in 28 genes with obesity risk in North Indian adults.

OBJECTIVES: The aim of the study was to investigate the association of 55 SNPs in 28 genes with obesity risk in a North Indian population using a multianalytical approach. METHODS: Overall, 480 subjects from the North Indian population were studied using strict inclusion/exclusion criteria. SNP Genotyping was carried out by Sequenom Mass ARRAY platform (Sequenom, San Diego, CA) and validated Taqman® allelic discrimination (Applied Biosystems® ). Statistical analyses were performed using SPSS software version 19.0, SNPStats, GMDR software (version 6) and GENEMANIA. RESULTS: Logistic regression analysis of 55 SNPs revealed significant associations (P < .05) of 49 SNPs with BMI linked obesity risk whereas the remaining 6 SNPs revealed no association (P > .05). The pathway-wise G-score revealed the significant role (P = .0001) of food intake-energy expenditure pathway genes. In CART analysis, the combined genotypes of FTO rs9939609 and TCF7L2 rs7903146 revealed the highest risk for BMI linked obesity. The analysis of the FTO-IRX3 locus revealed high LD and high order gene-gene interactions for BMI linked obesity. The interaction network of all of the associated genes in the present study generated by GENEMANIA revealed direct and indirect connections. In addition, the analysis with centralized obesity revealed that none of the SNPs except for FTO rs17818902 were significantly associated (P < .05). CONCLUSIONS: In this multi-analytical approach, FTO rs9939609 and IRX3 rs3751723, along with TCF7L2 rs7903146 and TMEM18 rs6548238, emerged as the major SNPs contributing to BMI linked obesity risk in the North Indian population.

Analysis of MC4R rs17782313, POMC rs1042571, APOE-Hha1 and AGRP rs3412352 genetic variants with susceptibility to obesity risk in North Indians.

BACKGROUND: Obesity is a multi-factorial disorder influenced by genetic and environmental factors. The physiological pathways associated with obesity are complex and involve several genes. AIM: The aim of this survey is to evaluate the association of genetic variants of melanocortin-4-receptor (MC4R), pro-opiomelanocortin (POMC), apolipoprotein E (APOE) and agouti-related protein (AGRP) with obesity in the North Indian population. METHODS: MC4R rs17782313, POMC rs1042571, APOE-Hha1 and AGRP rs3412352 polymorphisms were investigated for their association in 396 obese individuals with BMI ≥ 30 kg/m(2) and 300 healthy non-obese individuals with BMI < 30 kg/m(2). Genotyping was performed using Taqman probes and PCR-RFLP methods. Single locus logistic regression analysis was conducted using (SPSS), ver.19 and PLINK software Version 1.01 and high order genetic interactions associated with obesity risk were analysed using MDR software (version 2.3.0.2). RESULTS: The genotypes of MC4R rs17782313, POMC rs1042571 and APOE-Hha1 were significantly associated with obese individuals (BMI ≥ 30 kg/m(2)) when compared with non-obese individuals (BMI < 30 kg/m(2)). No association of AGRP rs34123523 was seen with obesity. CONCLUSIONS: The best interaction model for predicting obesity risk by MDR analysis was the three factor model including POMC (C > T), MC4R (T > C) and APOE (Hha1) polymorphisms. Genetic variants in MC4R, POMC and APOE genes might play significant roles in predisposing obesity (BMI ≥ 30 kg/m(2)) in the North Indian population.

Association of FTO and IRX3 genetic variants to obesity risk in north India.

BACKGROUND: Obesity is an increasingly important health problem worldwide as well as in developing countries like India. Recent genetic studies suggest that obesity associated FTO and IRX3 are functionally linked and many effects due to genetic variants in FTO gene act through IRX3. AIM: To evaluate the association of FTO and IRX3 genetic variants towards obesity risk. SUBJECTS AND METHODS: North Indian individuals categorised as non-obese (BMI < 30 kg/m(2)) and obese (BMI ≥ 30 kg/m(2)) were selected. FTO rs8050136, rs1421085, rs9939609, rs17817449 and IRX3 rs3751723 were genotyped by means of validated Taqman® allelic discrimination to evaluate their association with obesity by means of single locus logistic regression by SPSS ver. 19 and multi-locus linkage and haplotype analysis by SNPStats and gene-gene interaction with Generalised Multifactor Dimensionality Reduction (GMDR) ver.6. RESULTS: In single locus analysis, FTO rs8050136 CA (p = 0.0001; OR (95% CI) = 2.4 (1.7-3.4) and AA (p = 0.0001; OR (95% CI) = 3.1 (1.9-5.2); FTO rs1421085 TA (p = 0.0001; OR (95% CI) = 2.1 (1.4-3.0) and AA (p = 0.0001; OR (95% CI) = 3.0 (1.8-5.0); FTO rs9939609 TC (p = 0.0001; OR (95% CI) = 2.1 (1.5-3.1) and CC (p = 0.0001; OR (95% CI) = 4.2 (2.5-7.3) along with TG (p = 0.001; OR (95% CI) = 2.1 (1.3-3.2) and GG (p = 0.021; OR (95% CI) = 3.8 (1.2-11.8) genotypes of FTO rs17817449 with GT (p = 0.0001; OR (95% CI) = 2.1 (1.5-3.1) and TT (p = 0.012; OR (95% CI) = 3.3 (1.8-3.6) genotypes of IRX3 rs3751723 were significantly associated with obesity. In multi-locus analysis, SNPs of FTO and IRX3 were in strong linkage disequilibrium and in haplotype and GMDR analysis the SNPs were significantly associated with obesity risk (p < 0.05). CONCLUSION: This is the first study to reveal that genetic variants of both FTO and IRX3 genes are in high linkage disequilibrium (LD) and are associated with obesity risk in North Indians.

Genetics of Obesity.

Numerous classical genetic studies have proved that genes are contributory factors for obesity. Genes are directly responsible for obesity associated disorders such as Bardet-Biedl and Prader-Willi syndromes. However, both genes as well as environment are associated with obesity in the general population. Genetic epidemiological approaches, particularly genome-wide association studies, have unraveled many genes which play important roles in human obesity. Elucidation of their biological functions can be very useful for understanding pathobiology of obesity. In the near future, further exploration of obesity genetics may help to develop useful diagnostic and predictive tests for obesity treatment.

Interleukin-6 (IL-6)-597 A/G (rs1800797) & -174 G/C (rs1800795) gene polymorphisms in type 2 diabetes.

BACKGROUND & OBJECTIVES: Diabetes is a metabolic pro-inflammatory disorder characterized by chronic hyperglycaemia and increased levels of circulating cytokines suggesting a causal role for inflammation in its aetiology. In order to decipher the role of interleukin-6 (IL-6) in type 2 diabetes mellitus (T2DM) we analyzed two promoter polymorphisms -597 A/G (rs1800797) and -174 G/C (rs1800795) in T2DM cases from north India, and in healthy controls. METHODS: DNA was isolated from venous blood samples of T2DM patients (n=213) and normal healthy controls (n=145). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed after biochemical analysis. The genotypic and allelic frequency distributions were analyzed. RESULTS: The clinical/biochemical parameters of T2DM cases when compared to controls showed a significant difference. No significant association was observed with -597A/G polymorphism while, -174 G/C showed a highly significant association (P<0.001). In haplotypic analysis, combination of -597GFNx01/-174CFNx01 showed significant association (P=0.010). INTERPRETATION & CONCLUSIONS: Our data suggest that IL-6 gene polymorphisms play a prominent role in T2DM disease susceptibility in population from north India.

Association of IL-6, TNF-α and IL-10 gene polymorphisms with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a metabolic pro-inflammatory disorder characterized by chronic hyperglycemia and increased levels of circulating cytokines suggesting a causal role of inflammation in its etiology. Polymorphism of cytokine genes including interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were studied in T2DM patients as well as in normal healthy controls. Genomic DNA was isolated from both T2DM patients and controls followed by quantification and genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using suitable primers. The genotypic, allelic and carriage rate frequency distribution in patients and controls were analyzed by SPSS (version 15.0). Odd ratios with 95 % confidence interval was determined to describe the strength of association by logistic regression model. Double and triple combinations of genotypes were analyzed by χ(2) test. Gene-gene interaction and linkage disequilibrium tests were performed using SHEsis software. Individually, IL-6, TNF-α and IL-10 did not show any association. In double combination, IL-6 -597 GA and TNF-α -308 GG genotypes increased the risk up to 21 times and in triple combination IL-6 -597 AA, TNF-α -308 GG and IL-10 -592 CA increased the risk of T2DM up to 314 times. In gene-gene interaction allele 'A' of all studied polymorphisms increased the risk of T2DM up to 1.41 times. Our results suggest that individuals having a haplotype combination of AA, GG and CA for IL-6, TNF-α and IL-10 gene polymorphisms will have higher susceptibility and be at greater risk of developing T2DM.

Impact of CCL2 and Its Receptor CCR2 Gene Polymorphism in North Indian Population: A Comparative Study in Different Ethnic Groups Worldwide.

Chemokine are small, inducible pro-inflammatory cytokines involved in many biological processes, such as migration of leukocytes, atherosclerosis, angiogenesis, tumor growth, and metastasis. Chemokine are also known to influence tumor cell's activity. Specifically, tumor cells express chemokine receptors in a non random manner suggesting a role of chemokine in metastatic destination of tumor cells. The present study was conducted to determine distribution of (Chemokine receptor 2) CCR2 V64I, Chemokine ligand 2 CCL2 I/D, and CCL2 2518 A>G gene polymorphisms in North Indian population and compare with different populations globally. Polymerase chain reaction (PCR)-based analysis was conducted in 200 normal healthy individuals of similar ethnicity. Allelic frequencies in wild type (GG) of CCR2 V64I G>A were 63 % G; CCL2 I/D 42 % II; CCL2 2518 A>G 40.5 % A. The minor variant allele frequency in our population was as follows: 19.5 % for CCR2 V64I, 35.5 % for CCL2 I/D, 35.3 % for CCL2 2518 A>G. We further compared frequency distribution for these genes with various published studies in different ethnicity. Our results suggested that frequency in chemokine genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of human exposed to environmental carcinogens and cancer predisposition in different ethnic groups. Thus, they signify an impact of ethnicity and provide a basis for future epidemiological and clinical studies.

Hypoadiponectinemia in obesity: association with insulin resistance.

Obesity is risk factor for insulin resistance, diabetes, and other chronic diseases. Adiponectin, an adipose-specific protein with antiatherogenic and antiinflammatory effects, were found to be associated with obesity, type 2 diabetes, and insulin resistance. Our aim to identify possible relationships between circulating adiponectin and obesity as well as obesity related phenotypes. A total of 642, obese and non-obese individuals were included in this cross-sectional study. Hormone and glucose levels were estimated using standard protocols. The adiponectin levels showed a significant decrease with increasing quartiles of insulin resistance index. Subjects in lowest quartile of adiponectin level had a significantly higher risk than those in the highest quartile, with higher body mass index, waist circumference, blood pressure, percentage body fat, fat mass, fasting insulin, insulin resistance index, total cholesterol (p < 0.001), low density lipoprotein-cholesterol (p = 0.001), very low density lipoprotein-cholesterol (p = 0.002), and Triglyceride (p = 0.002). The present study indicates that adiponectin is significantly associated with obesity, insulin resistance and other obesity related phenotypes.

Association of apolipoprotein B XbaI gene polymorphism and lipid profile in northern Indian obese.

BACKGROUND: Over the last few decades, obesity, diabetes, and hypertension have become main health evils. The health problems of obesity are well-recognized. However, the fact that all obese individuals are not at the same risk of developing a disease is also recognized. The apolipoprotein B (APOB) plays a central role in lipid metabolism. So we compare the association of APOB XbaI gene polymorphism and lipid profile total in obese north Indian population. MATERIALS AND METHODS: A total of 132 obese (body mass index [BMI] >25 kg/m(2)) and 132 age matched non-obese (BMI ≤ 25 kg/m(2)) subjects were studied after taking detailed clinical profile. Lipid profile in serum/plasma was done using commercial kits. Genetic analysis of APOB XbaI was done using Polymerase Chain Reaction-Restriction Fragment Leanth polymorphism (PCR-RFLP). STATISTICAL ANALYSIS: Statistical analysis was performed by Statistical Package for the Social Sciences (SPSS) (version 11.5) software (IBM Corporation). All continuous variables were expressed as mean ± SD and tested by analysis of variance test. Comparisons of categorical variables were assessed using χ(2) tests or Fisher's exact test. P < 0.05 was considered as significant. RESULTS: Analysis showed that obese subjects had significantly higher value of the waist-to-hip ratio, blood pressure (systolic and diastolic), and lipid profile. In APOB XbaI gene polymorphism, we did not find significant differences in genotype or allele frequencies. Moreover, none of the studied metabolic parameters (lipid profile) showed any association with the gene polymorphism. CONCLUSIONS: Study reveals no considerable association of APOB XbaI gene polymorphism with obesity and lipid profile in north Indians.

Association of inflammatory chemokine gene CCL2I/D with bladder cancer risk in North Indian population.

Chemokine genes have been proposed as good candidate genes for conferring susceptibility to Bladder cancer (BC). We examined the combined effect of multiple alleles of pro inflammatory chemokine genes for determining the risk of BC. We tested association of three gene polymorphisms of CCL2I/D (rs3917887), CCL2A2518G (rs1024611) and CCR2V64I (rs1799864) with BC risk in North Indian population. Genotypes were assessed in hospital-based case-control study comprising of 200 BC patients and 200 healthy controls. Genomic DNA was isolated from blood and genotyping done using PCR-RFLP method. In CCL2I/D polymorphism, the heterozygous genotype (I/D) showed high risk of BC p < 0.001 OR = 2.56 and combination of ID + DD showed significant high risk for BC (p = 0.001 OR = 2.12). Haplotype analysis of CCL2I/D, CCL2A2518G gene polymorphisms demonstrated that combination of D-A was associated with 1.5-fold increased risk of BC. Variant genotype (DD) of CCL2I/D gene was associated with high risk of recurrence (p < 0.001 HR = 15.18) in superficial BC patients receiving BCG treatment thus showing least survival (log rank = 0.019). Our study suggested CCL2I/D polymorphism to be associated with higher BC risk and no contribution of CCR2V64I and CCL2A2518G genes. However, study with large sample size and diverse ethnicity is required to validate our observations.

Association of PPAR-γ gene polymorphisms with obesity and obesity-associated phenotypes in North Indian population.

OBJECTIVES: The worldwide increasing prevalence of obesity is considered as a major health problem. Peroxisome proliferator-activated receptor gamma (PPAR-γ) controls adipocyte differentiation and regulates a number of genes associated with energy homeostasis. In this study, we investigated the association of PPAR-γ gene Pro12Ala (rs1801282) and C1431T (rs3856806) polymorphisms with morbid obesity and related phenotypes, in north Indian population. METHODS: A total of 6,42 subjects, 309, obese and 333 nonobese individuals were included in this case-control study. Insulin, adiponectin, glucose, and lipid levels were estimated using standard protocols. All subjects were genotyped by PCR restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The ProAla+AlaAla genotypes of PPAR-γ Pro12Ala were significantly associated with higher risk of obesity while C1431T polymorphism did not show any significant association. None of the haplotypes showed association with morbid obesity. However, a strong association of variant genotypes was observed with higher levels of insulin, HOMA-IR, and lower serum adiponectin concentrations. CONCLUSION: PPAR-γ gene polymorphisms influence obesity and obesity phenotype in a complex manner, probably involving insulin resistance in north Indian population.

Effect of Yoga Nidra on physiological variables in patients of menstrual disturbances of reproductive age group.

Aim of this study was to see any effect on autonomic functions in menstrual disturbances patients after Yoga Nidra practice. The subjects for the study were 150 females with menstrual irregularities, 28.08 +/- 7.43 years of mean age, referred from department of Obstetrics and Gynecology CSMMU, UP, Lucknow. Subjects were divided randomly in to two groups' intervention and in control groups -seventy five (75) in each group. Out of these, one hundred twenty six (126) completed the study protocol. The yogic intervention consisted of 35-40 minutes/day, five days in a week till six months. An autonomic function testing was done in both the groups at zero time and after six months. A significant positive effect was observed when yoga therapy was used as an adjunct in the patients of menstrual disturbances. There were significant improvements in the blood pressure, postural hypotension and sustained hand grip, heart rate expiration inspiration ratio and 30:15 beat ratios of the subjects after yogic practice.

Association of sleep duration and sleep quality with body mass index among young adults.

Background: It is evident from the research in recent years that short sleep has been found as a risk factor for obesity. However, we still need enough evidence in this field. Therefore, we explored the directionality of the association between sleep duration and sleep quality with body mass index (BMI). Aims: The aim of this study is to evaluate the association of sleep duration and sleep quality with BMI among young adults. Objectives: (a) To assess the association of sleep duration with BMI. (b) To assess the quality of sleep with BMI. Methods: In this cross-sectional study, 88 individuals selected from King George's Medical University were taken as participants. Majority of patients were males (67%). There were 29 (33.0%) females. Sex ratio of study was 2.03, and we used Pittsburgh sleep quality index (PSQI) questionnaire to assess time spent in bed and sleep quality. BMI was divided into 3 categories. Underweight (BMI <18.5 kg/m2), normal weight (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), obese grade I (25-34.9 kg/m2), obese grade II (35.0 kg/m2), and above. Results: We observed that short sleep duration ± SD (h) <6 h/day f = 9.04; P < 0.001 is associated with greater chances of being overweight and obese and mean sleep quality (mean PSQI ± SD) f = 12.24; P < 0.001 was poor in obese grade I and II. Mean neck and waist circumference also showed a significant increasing trend with increasing BMI category (P < 0.001). Conclusion: This study concludes that short sleep duration and poor sleep quality were associated with overweight obesity among young adults.

The Origin and Clinical Relevance of Yoga Nidra.

Yoga nidra, also known as 'yogic sleep', is a simplified form of an ancient tantric relaxation technique. The most general description of the practice is that it combines guided mental imagery with a specific yoga posture called Shavasana (or "corpse pose"). The goal of yoga nidra is to promote a profound state of relaxation, which differs from sleep inasmuch as there is still an awareness of one's surroundings. While several components of the practice have been known since ancient times, it was not until the 1960s that an updated and systematized system of practice was introduced to the public through the writings of Swami Satyananda Saraswati. Unlike other schools of yoga, which emphasize concentration or contemplation, yoga nidra's goal is complete relaxation. As such, its advocates claim that it is suitable for all individuals, from beginners to advanced practitioners of yoga. The calm inner stillness induced by yoga nidra is claimed by practitioners to be an effective stress management tool as well as a means for attaining greater receptivity to personal resolutions. These resolutions can range from the goal of achieving self-transformation, enhancing creativity, or improving one's learning ability. Additionally, yoga nidra is claimed to promote beneficial changes in physiological and mental health. The following narrative review summarizes the basic steps used to achieve the final state of yoga nidra relaxation as well as some recent experimental findings regarding its physiological and psychological effects. Standard research databases were searched for relevant articles. Clinical studies have shown that yoga nidra meditation is associated with positive physiological changes, including improvements in several hematological variables, red blood cell counts, blood glucose levels, and hormonal status. Two neuroimaging studies have shown that yoga nidra produces changes in endogenous dopamine release and cerebral blood flow, a further confirmation that its effects on the CNS are objectively measurable. The practice has also been shown to reduce psychometrically measured indices of mild depression and anxiety, although these benefits were not shown in an experimental study to extend to severe depression or severe anxiety.

Association of FTO rs17817449 SNP with obesity and associated physiological parameters in a north Indian population.

BACKGROUND: Obesity is a very common disorder directly linked with various diseases such as type-2 diabetes, hypertension and atherosclerosis. Variants in the FTO gene have been associated with Body Mass Index in Western European and North American populations. AIM: This study analysed the association between the FTO gene variant rs17817449 (G>T) and obesity and obesity-related phenotypes in a north Indian population. SUBJECTS AND METHODS: A total of 642 subjects, 309 obese and 333 non-obese individuals, were included in this case-control study. Genotyping of FTO gene (rs17817449) polymorphism for all subjects was performed by the PCR-RFLP method. RESULTS: Significant associations were found for FTO rs17817449 SNP with obesity and obesity-related phenotypes. The strongest associations were observed between the rs17817449 and fasting blood glucose, insulin, homeostasis model of assessment--insulin resistance (HOMA-IR) and fat mass under a recessive model. CONCLUSIONS: This study replicated the genetic association of SNP of FTO (rs17817449) with obesity in a north Indian population and, to the authors' knowledge; this is the first such association study in a north Indian population. This study also established that SNP in intron 1 of FTO (rs17817449) are strongly associated with several measures of adiposity and are also associated with plasma insulin, insulin resistance, percentage body fat and fat mass.

A common polymorphism in the promoter of UCP2 is associated with obesity and hyperinsulenemia in northern Indians.

A polymorphism in the promoter region of uncoupling protein 2 gene -866 G/A has been associated with its expression levels, the risk of obesity, and metabolic abnormalities. We aimed to investigate the associations of uncoupling protein (UCP)2 gene variants with obesity and related traits. A total of 440 subjects, 200 obese, and 240 non-obese individuals were included in this case-control study. Hormone and glucose levels were estimated using standard protocols. Genotyping of UCP-2 gene polymorphism for all subjects was performed by the PCR-RFLP polymerase chain reaction (PCR) method. Higher Systolic blood pressure, Diastolic blood pressure, Waist to hip ratio, Leptin, Insulin, and blood glucose levels were observed in obese than non-obese (P < 0.05). The distributions of genotype (0.001) and allele (0.003) were significantly different between the non-obese and the obese groups. In the obese group, subjects with the A allele showed significant high insulin levels (<0.001) in comparison with A allele non-carriers. In conclusion, our results suggest that the -866 AA genotype and A allele of the UCP2 gene is associated with obesity and A allele associated with hyperinsulinemia in obese subjects.

Association of beta2-adrenergic receptor and insulin receptor substrate-1 polymorphisms with obesity in a Northern Indian population.

BACKGROUND: Imbalance in hormonal levels, regulated by host genetic factors, are known to be a major cause of obesity. Therefore, we aimed to evaluate association of genetic polymorphisms of beta(2)-adrenergic receptor (beta(2)-AR) and insulin receptor substrate-1 (IRS-1) with hormonal levels in northern Indian obese. METHODS: A total of 111 obese and 89 age matched non-obese subjects were studied after taking detailed clinical profile. Hormonal assays in serum/plasma for different hormones were done using IRMA and RIA kits. Genetic analysis of beta(2)-AR (-47 and -20, T to C) and IRS-1 (Arg972Gly) was done using PCR-RFLP. STATISTICAL ANALYSIS: Statistical analysis was performed by SPSS (version 11.5) software. All continuous variables were expressed as mean +/- SD and tested by ANOVA test. Comparisons of categorical variables were assessed using X(2) tests or Fisher's exact test. P-value <0.05 was considered as significant. RESULTS: Analysis showed that obese subjects had significantly higher value of blood pressure (systolic), WHR, leptin insulin and glucagon and lower value of GH. In beta(2)-AR (-47) T/C and IRS-1 Gly972Arg gene polymorphisms we did not found significant differences in genotype or allele frequencies. Moreover, none of the studied hormonal or metabolic parameters showed any association with the gene polymorphisms. CONCLUSIONS: Study reveals no significant association of beta(2)-AR (-47 and -20, T to C) and IRS-1 Gly 972 Arg polymorphisms with obesity in northern Indians.

Cytokine Gene Variants as Predictors of Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes is the third widespread after heart disease and cancer. We have investigated genetic polymorphisms in cytokine genes viz. IL-4, IL-1Ra, IL-1ß, IL-18, IL-6, TNF-α, IL-10 and ADIPOQ. The aim of study was to investigate the haplotypes, gene-gene interactions and their role in determining individual susceptibility to T2DM of family members with diabetic history. METHODS: Haplotype analysis of 2 SNPs each in IL-6 and adiponectin genes showing Pairwise Linkage disequilibrium (LD) was done by SHEsis software. Logistic regression was used to study various combinations of gene-gene interactions. RESULTS: The TCGT* set of allele combination appeared to increase the disease risk upto 2 times while TATG* upto 51.4 times when four SNPs are taken together viz. IL-1ß-511 C/T, IL-18-607 A/C, ADIPOQ1 +45 G/T and ADIPOQ2 +10211 T/G. Interaction of SNPs in eight genes showed one highly significant combination of alleles, TCGAGCTT* which increased the risk of T2DM upto 7.4 times while CAGAGCGT* allele combination increased the risk upto 4 times. CONCLUSION: During pedigree analysis in six families with four SNPs, it was interesting to note that susceptible 'AC' genotype of IL-18-607 A/C was frequent in diabetic individuals in almost all families. Moreover, when checked for the presence of risk haplotypes it was observed that TCGT* and TATG* sets of allele combinations were present in most of the diabetic individuals. Individuals with certain abnormal biochemical parameters but not yet diagnosed for T2DM carried the risk genotype or haplotype. This suggested that individuals carrying risk genotypes/haplotypes might be susceptible to T2DM and develop the disease in the future.