North Indian Subjects Research Articles

Clinic-morphological indicators to diagnose hypertriglycedemia the importance of mid abdominal circumference as a screening tool

Objective: To find a cut off level of mid abdominal circumference in North Indian subjects to use as a predictive tool for diagnosing individuals with raised serum triglyceride levels. Methods: This was a cross-sectional hospital based study conducted over a period of three years at Vivekananda Polyclinic and Institute of Medical Sciences, Lucknow, India. Not known cases of dyslipedimia were included in this study attending in the out-patient clinic of the hospital. The subjects were screened for overnight fasting (for 8 to 12 hrs) levels of triglycerides after asking them to be on a normal diet for three days. A total of 857 subjects were included in the study. Results: One forth (25%) of the subjects were in the age group 40-49 years. The mean age was 54.57 years. More than half (53.3%) of the subjects were males and were vegetarian (63%). Less than one third (28.6%) of the subjects were alcoholic and 39% were smokers. The mean abdominal girth was 106.25 (±11.07) cms and height was 161.46 (±6.68). However, average weight was 69.38 (±9.66) kg and TG level was 205.08 (±55.80). Linear regression analysis showed that the cut off of 92 cms was obtained for male and 93 cms for females. Above this abdominal girth, an increased TG levels will be with a high rate of sensitivity and specificity for both the sexes.

Assessment of iodine nutrition in pregnant north Indian subjects in three trimesters

Objective:The cross-sectional study was carried out to assess the iodine status of pregnant women, using median urinary iodine concentration (MUI) as the measure of outcome, to document the impact of advancing gestation on the MUI in normal pregnancy.Materials and Methods:The present study assessed the MUI in casual urine samples from 50 pregnant subjects of each trimester and 50 age-matched non-pregnant controls.Results:The median (range) of urinary iodine concentration (UIC) in pregnant women was 304 (102-859) μg/L and only 2% of the subjects had prevalence of values under 150 μg/L (iodine insufficiency). With regard to the study cohort, median (range) UIC in the first, second, and third trimesters was 285 (102-457), 318 (102-805), and 304 (172-859) μg/L, respectively. Differences between the first, second, and third trimesters were not statistically significant. The MUI in the controls (305 μg/L) was not statistically different from the study cohort.Conclusion:The pregnant women had no iodine deficiency, rather had high median urinary iodine concentrations indicating more than adequate iodine intake. Larger community-based studies are required in iodine-sufficient populations, to establish gestation-appropriate reference ranges for UIC in pregnancy.

Functional genetic variants of CTLA-4 and risk of tobacco-related oral carcinoma in high-risk North Indian population

Single nucleotide polymorphisms (SNPs) of the CTLA-4 gene have been implicated in susceptibility to different cancer in different ethnic populations. We assessed the association of five SNPs [-1722C/T, -1661A/G and -318C/T in the promoter region49A/G in exon 1 and CT60A/G in the 3'untranslated region (UTR)] with tobacco-related oral squamous cell carcinoma (OSCC) in North Indian subjects. We genotyped 130 OSCC patients and 180 normal subjects by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) using BbvI, MseI, NcoI and BstEII restriction endonucleases. Among these SNPs, -1722CC, -1661AG and CT60AA genotypes were more prevalent in OSCC patients as compared to controls and in the logistic regression analysis with odd ratio (OR) 2.85, 95% CI (0.69-11.68); OR 2.48, 95% CI (1.29-4.78) and OR 3.0, 95% CI (1.43-6.28) respectively, these genotypes showed strong association with OSCC risk. With higher prevalence in controls 49GG genotype and G allele (OR 0.57, 95% CI 0.40-0.81) appeared to be protective. Moreover, TACAG, TACGA and TATAG appeared as susceptible while TACGG and CACGG appeared as protective haplotypes. These results suggest significant risk modifying effects of CTLA-4 -1722C/T, -1661A/G, -318T/C, CT60 A/G and 49A/G SNPs in tobacco-related OSCC in North Indian population.

The association of non-HDL cholesterol with the presence of metabolic syndrome in North Indian subjects with and without CAD

Aim: The present study aims to identify which lipid parameter is significantly associated with Coronary Artery Disease (CAD) and metabolic syndrome (MetS) and also to find out the association of non-HDL cholesterol (non-HDL-C) with the presence of MetS in North Indian subjects with and without CAD.Subjects and methods: One hundred and thirteen CAD and 140 non-CAD (controls) aged 35–75 years were recruited for the study, matched for ethnicity and geography after obtaining their written informed consent. The CAD patients were identified based on their medical diagnostic history. Height, weight, waist and hip circumferences, blood pressures (systolic and diastolic) and lipid profile were measured for all the subjects.Results: Sixty-nine out of 113 (61.06%) of CAD and 52/140 (37.1%) of non-CAD had MetS. Age standardized prevalence of MetS was 23.2% and 16.1% in CAD and non-CAD individuals, respectively. Age standardized prevalence of metabolic abnormalities in the CAD group was in the order of abdominal obesity>non-HDL-C>systolic blood pressure (SBP) > triglyceride (TG) > total cholesterol (TC) > diastolic blood pressure (DBP) > Low Density Lipoprotein Cholesterol (LDL-C) > High Density Lipoprotein Cholesterol (HDL-C). Non-HDL-C, TG and HDL-C were found to be significantly associated with MetS.Conclusions: TG and HDL-C are established risk components included in the characterization of MetS; but significant association of non-HDL-C with MetS in the present study is a key finding. The study focuses on the use of non-HDL-C as a simple screening tool to identify individuals with clustering metabolic abnormalities which increase the propensity for CAD.

Soft-tissue cephalometric norms for north Indian Mongoloids

IntroductionHarmonious facial esthetics and functional occlusion have long been recognized as the two most important goals of orthodontic treatment. The purpose of this study was: (1) To establish soft tissue cephalometric norms for Mongoloid tribes of north India using Holdaway analysis. (2) To study the sexual dimorphism in soft tissue cephalometric norms of this population. (3) To compare the norms obtained in this study with Holdaway norms. MethodsLateral cephalometric radiographs of 60 north Indian Mongoloid subjects (30 male, 30 female) in the age group of 18–25years with normal occlusion and well balanced faces were used. The cephalograms were analyzed with Holdaway soft tissue cephalometric analysis. Unpaired t-test was used to compare results obtained for Mongoloid subjects with Holdaway norms and to determine sexual dimorphism. ResultsStatistically significant differences were found for nose prominence, superior sulcus depth, soft tissue subnasale to H-line, basic upper lip thickness, max incisor to upper lip, H-angle, lower lip to H-line and soft tissue chin thickness. In comparison of sexes, statistically significant differences were found for basic upper lip thickness, max incisor to upper lip and H-angle. ConclusionThese results show that the soft tissue facial profile of north Indian Mongoloid subjects and North-Europeans are different. These racial differences must be considered during diagnosis and treatment planning.

Poster #109 NEURO-IMMUNE CROSSTALK: GENETIC UNDERPINNINGS OF IMMUNE SYSTEM ACTIVATION WITH RESPECT TO FRONTAL LOBE COGNITIVE FUNCTIONS IN SCHIZOPHRENIA

Single nucleotide polymorphisms (SNPs) of the CTLA-4 gene have been implicated in susceptibility to different cancer in different ethnic populations. We assessed the association of five SNPs [−1722C/T, −1661A/G and −318C/T in the promoter region49A/G in exon 1 and CT60A/G in the 3′untranslated region (UTR)] with tobacco-related oral squamous cell carcinoma (OSCC) in North Indian subjects. We genotyped 130 OSCC patients and 180 normal subjects by polymerase chain reaction- restriction fragment length polymorphism (PCR-RFLP) using BbvI, MseI, NcoI and BstEII restriction endonucleases. Among these SNPs, −1722CC, −1661AG and CT60AA genotypes were more prevalent in OSCC patients as compared to controls and in the logistic regression analysis with odd ratio (OR) 2.85, 95% CI (0.69–11.68); OR 2.48, 95% CI (1.29–4.78) and OR 3.0, 95% CI (1.43–6.28) respectively, these genotypes showed strong association with OSCC risk. With higher prevalence in controls 49GG genotype and G allele (OR 0.57, 95% CI 0.40–0.81) appeared to be protective. Moreover, TACAG, TACGA and TATAG appeared as susceptible while TACGG and CACGG appeared as protective haplotypes. These results suggest significant risk modifying effects of CTLA-4 −1722C/T, −1661A/G, −318T/C, CT60 A/G and 49A/G SNPs in tobacco-related OSCC in North Indian population.

The epistasis between vascular homeostasis genes is apparent in essential hypertension

Objective The epistasis influence of vascular homeostasis genes is vital to multigenetic diseases. This study was designed to perceive the possible role of epistasis in the etiology of essential hypertension. Methods We investigated seven polymorphisms of ACE, CYP11B2 and NOS3 epistatically, and SBP, DBP, MAP, ACE activity, plasma aldosterone concentration (PAC) and NOx level in 860 age- and ethnicity-matched unrelated north-Indian subjects. Results The hypertension risk in individuals with interacted-genotypes (IwIw + IwIc) + (4aa), (IcIc) + (4bb + 4ba) and IcIc + 4aa of the CYP11B2 and NOS3 was significantly higher with odds ratio 5.5 (95% CI = 2.9–10.6, P < 0.0001), 2.4 (95% CI = 1.4–4.1, P < 0.0008) and 7.5 (95% CI = 1.6–34.8, P = 0.010), respectively. The odds ratio for hypertension with interacted-haplotypes (−344T/Ic) + (−922A/−786T/4a/894G) and (−344T/Ic) + (−922G/−786C/4a/894G) of CYP11B2 and NOS3 was 5.3 (95% CI = 2.0–14.2, P = 0.005) and 3.9 (95% CI = 1.4–10.4, P = 0.04), respectively; whereas for the protective interacted-haplotypes (−344T/Iw) + (−922A/−786T/4b/894G), the odds ratio was 0.7 (95% CI = 0.5–0.9, P = 0.03). While the interacted-genotypes, IcIc + 4aa correlated with higher SBP and MAP ( P = 0.006; P = 0.04), the interacted-haplotypes, (−344T/Ic) + (−922A/−786T/4a/894G) and (−344T/Ic) + (−922G/−786C/4a/894G) correlated with higher MAP and lower NOx level ( P = 0.02 and P = 0.03, respectively), and the protective interacted-haplotypes (−344T/Iw) + (−922A/−786T/4b/894G) correlated with lower PAC and MAP ( P = 0.024 and P = 0.018, respectively). Conclusions The epistasis between CYP11B2 and NOS3 and its correlation with varied clinical and biochemical parameters signify its possible contribution in the complex etiology of hypertension.

Evaluation of DOK5 as a susceptibility gene for type 2 diabetes and obesity in North Indian population

BackgroundType 2 diabetes is a complex metabolic disorder with obesity being a major contributing factor in its development. Susceptibility loci for type 2 diabetes and obesity have been localized on different chromosomal regions by various genome-wide linkage scans. Of these chromosomal regions, 20q13 is one of the strongest linked regions for type 2 diabetes as well as obesity. On 20q13 lies DOK5 that seems to be a strong functional and positional candidate for type 2 diabetes and obesity because of its involvement in insulin signaling and immune responses. Hence, for the first time, we explored DOK5 as a potential type 2 diabetes and obesity susceptibility gene.MethodsWe sequenced 43 subjects for polymorphisms in functionally relevant regions of DOK5. A total of 10 SNPs that included 5 that were identified by sequencing and 5 additional SNPs from NCBI Variation Database were genotyped in 2,115 participants comprising of 1,073 patients with type 2 diabetes and 1,042 controls of Indo-European ethnicity from North India.ResultsWe identified a novel variant in intron 7 referred to as DK176673. We found nominal association of three SNPs-rs6064099 (OR = 0.75, P = 0.019), rs873079 (OR = 0.76, P = 0.036) and DK176673 (OR = 1.55, P = 0.037) with type 2 diabetes among normal-weight subjects [BMI < 23 kg/m2]. The haplotype GGC harboring rs6068916, rs6064099 and rs873079 showed strong association with type 2 diabetes among normal-weight subjects (OR = 1.37, P/Pperm = 5.8 × 10-3/0.037). Association analysis with obesity revealed that rs6064099 is associated with reduced susceptibility for obesity (OR = 0.48, P = 6.8 × 10-3). Also, haplotype GGC conferred increased susceptibility for obesity (OR = 1.27, P/Pperm = 9.0 × 10-3/0.039). Also, rs6064099 was significantly associated with reduced BMI [median(IQR) = 24.0(20.7-27.1) vs 23.9(20.2-26.8) vs 21.8(19.2-24.7) for GG vs GC vs CC, P = 7.0 × 10-3].ConclusionsWe identified DOK5 as a novel susceptibility gene for obesity and type 2 diabetes in North Indian subjects. Association of DOK5 variants both with obesity and type 2 diabetes suggests that these variants might modulate type 2 diabetes susceptibility through obesity.

Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in Indian males: a preliminary study

BackgroundDopamine is an important neurotransmitter involved in reward mechanism in the brain and thereby influences development and relapse of alcohol dependence. The dopamine D2 receptor (DRD2) gene on chromosome 11 (q22-q23) has been found to be associated with increased alcohol consumption through mechanisms involving incentive salience attributions and craving in alcoholic patients. Therefore, we investigated the association of three single nucleotide polymorphisms (SNP) in DRD2 gene with alcohol dependence in the north Indian subjects.MethodsIn a retrospective analysis, genetic association of three polymorphisms from DRD2 gene with alcohol dependence was investigated using a case-control approach. Alcohol dependence was determined by DSM-IV criteria and a total of 90 alcoholics and 60 healthy unrelated age-matched control subjects were recruited. Odds ratio and confidence interval was calculated to determine risk conferred by a predisposing allele/genotype/haplotype. Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair-wise interactions between SNPs.ResultsThe study showed a significant association of -141C Ins allele and a trend of association of TaqI A1 allele of DRD2 with alcohol dependence. Haplotype with the predisposing -141C Ins and TaqI A1 alleles (-141C Ins-A-A1) seems to confer ≈ 2.5 times more risk to develop alcohol dependence.ConclusionsThe study provides preliminary insight into genetic risk to alcohol dependence in Indian males. Two polymorphisms namely, -141C Ins/Del and TaqI A in DRD2 gene may have clinical implications among Indian alcoholic subjects.

Association of homocysteine and methylene tetrahydrofolate reductase (MTHFR C677T) gene polymorphism with coronary artery disease (CAD) in the population of North India

The implications of the methylene tetrahydrofolate reductase (MTHFR) gene and the level of homocysteine in the pathogenesis of coronary artery disease (CAD) have been extensively studied in various ethnic groups. Our aim was to discover the association of MTHFR (C677T) polymorphism and homocysteine level with CAD in north Indian subjects. The study group consisted of 329 angiographically proven CAD patients, and 331 age and sex matched healthy individuals as controls. MTHFR (C677T) gene polymorphism was detected based on the polymerase chain reaction and restriction digestion with HinfI. Total homocysteine plasma concentration was measured using immunoassay. T allele frequency was found to be significantly higher in patients than in the control group. We found significantly elevated levels of mean homocysteine in the patient group when compared to the control group (p = 0.00). Traditional risk factors such as diabetes, hypertension, smoking habits, a positive family history and lipid profiles (triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol), were found significantly associated through univariate analysis. Furthermore, multivariable logistics regression analysis revealed that CAD is significantly and variably associated with diabetes, hypertension, smoking, triglycerides and HDL-cholesterol. Our findings showed that MTHFR C677T polymorphism and homocysteine levels were associated with coronary artery disease in the selected population.

Middle finger length — a predictor of stature in the Indian population

Stature is an important indicator for identification. There are numerous means to establish stature and their significance lies in the simplicity of measurement, applicability and accuracy in prediction. The present study was conducted on 500 north and south Indian subjects in Manipal, India, to establish the stature of an individual using the middle finger length. Measurements were analysed statistically to establish the relationhip between a person's middle finger length and their stature. The study shows that the middle finger length bears a significant relation to stature and can be an important tool for stature estimation. Significant differences in measurements and formulae for males and females were found. These differences were insignificant when values were compared between subjects of the same sex in north and south Indians and also between the dominant and non-dominant hand.

Association of cholesteryl ester transfer protein (TaqIB) and apolipoprotein E (HhaI) gene variants with obesity

Background The pathophysiology of obesity is known to be influenced by alterations in lipid levels. We aimed to evaluate association of cholesteryl ester transfer protein (CETP) and apolipoprotein (APO) E gene variants with asymptomatic obesity. Methods A total of 437 subjects, 159 asymptomatic obese (BMI = 29.29 +/- 3.76) and 278 non-obese (BMI = 23.38 +/- 1.71) individuals, were included in this case-control study. Lipid levels were estimated using standard protocols. Analysis of CETP (TaqIB) and APOE (HhaI) gene polymorphisms was done using PCR-RFLP. Results We found significant difference in blood pressure (systolic, P < 0.0001 and diastolic, P < 0.0001), total cholesterol (P < 0.0001), LDL-cholesterol (P < 0.0001), and HDL-cholesterol (P < 0.0001) in obese as compared to non-obese group. Homozygous APO E4E4 genotype was only observed in 5.7% of obese individuals and none in non-obese group. APO E4 allele carriers were also susceptible for obesity (P = 0.016, OR = 1.73; 95% CI = 1.12-2.68) than non-carriers. Higher blood pressure (Systolic, P = 0.001 and Diastolic, P = 0.004) and triglyceride levels (P = 0.029) were observed in obese subjects with APO E4 allele than individuals without APO E4. However, CETP B1 variant allele carriers did not show alteration in blood pressure and lipid profile in asymptomatic obese subjects. Conclusions APO E4 genotype and allele were found to be associated with asymptomatic obesity, whereas CETP Taq1B polymorphism showed no such association in North Indian subjects.

Oxidative stress pathway genes and chronic renal insufficiency in Asian Indians with Type 2 diabetes

Background There are significant regional variations in prevalence of diabetes and diabetic chronic renal insufficiency (CRI) in India. Oxidative stress plays an important role in the development of diabetic complications. To determine the importance of the polymorphisms in the genes involved in maintenance of cellular redox balance, we performed a case control study in subjects from south and north India. Methods Successive cases presenting to the study centers with Type 2 diabetes of >2 years duration and moderate CRI ( n=194, south India 104, north India 90) diagnosed by serum creatinine ≥2 mg/dl after exclusion of nondiabetic causes of CRI were compared with diabetes subjects with no evidence of renal disease ( n=224, south India 149, north India 75). Twenty-six polymorphisms from 13 genes from the oxidative stress pathway were analyzed using polymerase chain reaction–restriction fragment length polymorphism. Genes included were superoxide dismutases (SOD1, 2, 3), uncoupling proteins (UCP1, 2), endothelial nitric oxide synthase (NOS3), glutathione- S-transferases (GST) (M1, T1, P1), vascular endothelial growth factor (VEGF), paraoxonase (PON) 1 and 2, and nicotinamide adenine dinucleotide phosphate reduced, oxidase p22 phox. Genes were tested for their association with CRI using χ 2 test. Results In south Indian (SI) subjects there was significant allelic and genotypic association of the wild-type allele in SOD2 (Ala9Val; P=.002 and P=.013, respectively), UCP1 (−112 T>G, P=.012 and P=.009; Ala64Thr, P=.015 and P=.004), NOS3 (Glu298Asp, P=.002 and P=.009) and GSTP1 (Ile105Val, P=.003 and P=.004) genes with development of CRI. None of these observations were replicated in the north Indian (NI) subjects. A genotypic but not allelic association was observed for two markers, VEGF (−460 T>C) and PON1 (Arg192Gly) among NI diabetic CRI subjects. Conclusion The nonreplication of association suggests differential genetic susceptibility of the two populations to diabetic chronic renal insufficiency. In the SI diabetic subjects, oxidative stress pathway genes might be an important predictor for the development of diabetic complications. Further, the association of wild-type alleles may suggest that they confer greater survival ability to comorbid complications and may be nephroprotective.

A study of homocysteine level in North Indian subjects with special reference to their dietary habit

Summary Background & aim Dietary habit may influence homocysteine (Hcy) level and there is paucity of such studies from Northern India. This study was carried out to study Hcy levels in normal volunteers and compare these with dietary habits, plasma B12 and folic acid. Methods In a cross-sectional study, 200 normal volunteers were subjected to evaluation of demographic (age, gender, dietary habit and physical activity), clinical (body mass index, blood pressure, smoking and alcohol) and laboratory (plasma B12, folic acid and Hcy) parameters. The Hcy levels were compared in vegetarians and non-vegetarians and correlated with various demographic, clinical and laboratory findings. Results The mean age of the subjects was 39.4(18–73) years and 76 were females. A total of 27 were sedentary, 36 smokers and 30 took alcohol. Body mass index was high in 36 and 99 were lacto-vegetarians. Plasma Hcy level in vegetarians was significantly higher (20.42±12.98 μmol/L) compared to non-vegetarians (16.43+10.66 μmol/L). Plasma B12 and folic acid levels, however, were insignificantly lower in vegetarians. On multivariate analysis hyperhomocysteinemia was related to low plasma vitamin B12 level only. Conclusion In vegetarians Hcy levels were higher than non-vegetarians and were related to low plasma B12 level.

Distribution of CCR2 polymorphism in HIV‐1‐infected and healthy subjects in North India

Substitution of V64I in CCR2 relates to delayed progression to AIDS and protects against HIV-1 infection. We examined the distribution of V64I in HIV-infected and healthy North Indian subjects. No significant difference in the allele or genotype distribution of CCR2 V64I polymorphism was observed, indicating that there is no association between CCR2 V64I polymorphism and susceptibility to HIV infection in North Indian population.

Impact of polymorphism in sulfotransferase gene on the risk of lung cancer

Sulfotransferases (SULTs) are very important multifunctional enzymes that catalyze sulfonate conjugation, which is an important pathway in the phase II metabolism of numerous endogenous and exogenous compounds. Sulfotransferase 1A1 (SULT1A1) is active toward a wide range of substrates, including environmental and tobacco carcinogens. This case-control study involved collection of peripheral blood samples (2–5 mL) of 103 lung cancer patients and 122 controls from North Indian subjects. The SULT1A1 polymorphism was determined by using a polymerase chain reaction–restriction fragment length polymorphism method. The association between polymorphisms in the SULT1A1 gene with the risk of lung cancer was estimated by computing odds ratios (OR) and 95% confidence intervals (95% CI), using a multivariate logistic regression analysis. We observed marginally increased risk for mutant genotype (AA) of SULT1A1 for lung cancer (OR = 1.4, 95% CI = 0.48–4.06). A statistically significant association was found for smokers between either of two SULT1A1 genotypes, GA (OR = 10.3, 95% CI = 3.48–31.78, P = 0.000002) or AA (OR = 3.9, 95% CI = 1.99–7.81, P = 0.0002), and lung cancer. The present study indicates that the SULT1A1 genotype may play an important role in the risk of developing lung cancer, especially in cigarette smokers.

CYP2D6 phenotyping in North Indian subjects in Delhi

The recognition of the importance of inter-subject variation in drug metabolism has increased markedly over the past 20 years. Inter-subject variation may be genetically determined, environmentally induced, or most commonly, a combination of both, resulting in genetic polymorphism. The objective of the present study is to examine the CYP2D6 phenotypes in north Indian population. The study was carried out on seventy-five unrelated healthy north Indian subjects. They were phenotyped with respect to their ability to metabolize dextromethorphan to dextorphan. Oral dextromethorphan (30 mg) was administered to each subject. Urine was collected during 0 to 8 h period after dosing and was analyzed for dextromethorphan and dextorphan by liquid chromatography mass spectrometry (LC-MS/MS). The log 10 (metabolic ratio), calculated as the ratio of dextromethorphan to dextorphan, was bimodally distributed. An antimode value of 0.3 was obtained by plotting a frequency histogram of the log metabolic ratios. The frequency of occurrence of poor metabolizers of dextromethorphan in north Indian subjects from Delhi was found to be 2.6%. Ethiopian Pharmaceutical Journal Vol. 24, 2006: 65-70

Promoter region ‐318 C/ T and ‐1661 A/G CTLA‐4 single nucleotide polymorphisms and type 1 diabetes in North Indians

Single nucleotide polymorphisms (SNPs) of the CTLA-4 gene have been associated with manifestation of type 1 diabetes in several populations. We assessed the association of five SNPs present in the CTLA-4 gene [-318C/T, -1661A/G and -1722C/T in the promoter region, +49A/G in exon 1 and CT60 in the 3' untranslated region (UTR) region] with type 1 diabetes in North Indian subjects. Genotyping was performed in the patients (n = 130) and the healthy control (n = 180) subjects by polymerase chain reaction-fragment length polymorphism analysis using MseI, BbvI, BstEII and NcoI restriction endonucleases for the -318, -1661, -1722, +49 and CT60 SNPs, respectively. The frequency of G alleles at -1661 locus was significantly higher in the patient group compared with the control subjects. Although the frequency of T alleles at -318 SNP was significantly higher in patients with type 1 diabetes compared with the controls, it did not remain significant after Bonferroni correction for the number of alleles tested. The frequencies of C/T alleles and genotypes at -1722C/T and G allele at +49A/G and CT60 SNPs were not significantly different between the patient and the control groups. Of the various possible haplotypes constructed using the five genetic loci tested (-318, -1661, -1722, +49, CT60), the frequency of 'TGTAG' haplotype was significantly higher in the patients when compared with the controls. The results of the present study indicate that the presence of G allele at -1661 locus at the CTLA-4 gene (IDDM12 locus) is associated with increased susceptibility to type 1 diabetes in North Indians, whereas A allele is protective.

β 2 -adrenergic receptor polymorphisms and asthma in the North Indian population

The beta(2)-adrenergic receptor (ADRB2) polymorphisms are known to be functionally relevant and disease modifying in subjects with asthma. However, the association of these polymorphisms with asthma remains to be established. Our objective is to investigate the association of the ADRB2 polymorphisms and haplotypes with asthma in North Indian subjects. A subset of 101 unrelated cases and 55 unrelated unaffected individuals were used for a case-control disease-association test. Ten variable single nucleotide polymorphism (SNP) sites within a span of 2.193 kb were identified in the ADRB2 gene by the sequencing and genotyping of 351 bronchial asthma patients and healthy individuals. The distributions of genotype and allele frequencies for individual SNPs in the ADRB2 gene and ADRB2 haplotype frequencies were estimated in unrelated asthmatics and healthy individuals. No significant association was observed between ADRB2 genotypes and alleles with disease status after Bonferroni correction for multiple testing (reference p value = 0.0083). However, haplotype GGCTTTGCAA was found to be significantly associated with asthma (p = 0.021) in the studied population. Our results suggest that there is likely to be a functional significance of the ADRB2 gene with asthma.

Orthopedic and orthodontic effects of Twin-block appliance

This prospective study was conducted on 24 North Indian subjects (10 Control and 14 Twin-block) to evaluate the skeletal and dentoalveolar effects of Twin-block appliance in the treatment of Class II division 1 malocclusion. The result of the present study showed that Twin-block is an effective appliance in accelerating mandibular growth. It also helped dramatically in molar correction and overjet reduction in Class II division 1 malocclusion subjects.