Kidney Organoids Generated Using an Allelic Series of NPHS2 Point Variants Reveal Distinct Intracellular Podocin Mistrafficking.

BACKGROUND: NPHS2 variants are the most common cause of steroid-resistant nephrotic syndrome in children >1 month old. Missense NPHS2 variants were reported to cause mistrafficking of the encoded protein, PODOCIN, but this conclusion was on the basis of overexpression in some nonpodocyte cell lines. METHODS: We generated a series of human induced pluripotent stem cell (iPSC) lines bearing pathogenic missense variants of NPHS2 , encoding the protein changes p.G92C, p.P118L, p.R138Q, p.R168H, and p.R291W, and control lines. iPSC lines were also generated from a patient with steroid-resistant nephrotic syndrome (p.R168H homozygote) and a healthy heterozygous parent. All lines were differentiated into kidney organoids. Immunofluorescence assessed PODOCIN expression and subcellular localization. Podocytes were transcriptionally profiled and PODOCIN-NEPHRIN interaction interrogated. RESULTS: All variant lines revealed reduced levels of PODOCIN protein in the absence of reduced transcription. Although wild-type PODOCIN localized to the membrane, distinct variant proteins displayed unique patterns of subcellular protein trafficking, some unreported. P118L and R138Q were preferentially retained in the endoplasmic reticulum (ER); R168H and R291W accumulated in the Golgi. Podocyte profiling demonstrated minimal disease-associated transcriptional change. All variants displayed podocyte-specific apoptosis, which was not linked to ER stress. NEPHRIN-PODOCIN colocalization elucidated the variant-specific effect on NEPHRIN association and hence NEPHRIN trafficking. CONCLUSIONS: Specific variants of endogenous NPHS2 result in distinct subcellular PODOCIN localization within organoid podocytes. Understanding the effect of each variant on protein levels and localization and the effect on NEPHRIN provides additional insight into the pathobiology of NPHS2 variants. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_01_05_JASN2022060707.mp3.

Ethnic heterogeneity in body composition patterning and CVD risk factors: a multi-ethnic study of Asian Indian Tribes.

BACKGROUND: Indian subcontinent exhibits considerable degree of ethnic heterogeneity in cardiovascular disease (CVD) risks. Given the importance of ethnicity, the present multi-ethnic study was conducted to find out the differences in body composition patterning and its influence on CVD risk variables. OBJECTIVE: Owing to considerable ethnic heterogeneity among Asian Indians the study was performed to determine the association of variability between body composition and CVD risk factors at the micro-level among different tribes by sex, province, and generation. METHODS: Nine tribes from three different states (provinces) were considered. Anthropometric measurements, body composition, adiposity, blood pressure, and fasting blood glucose was measured using standard technique. Body composition was measured using BIA method by means of body fat monitor. Mean differences of the body composition measures were analysed by ANOVA. Stepwise multiple regressions were done with CVD risk variables as dependent and body composition profiles as independent variables to find out the significant predictors. Those were then loaded for principal component factor analyses (PCFA). RESULTS: Tribal subjects of both sexes and from both younger and older generations in Gujarat had significantly higher percentage body fat, subcutaneous fat-whole body, and subcutaneous fat-trunk as compared to tribal subjects of Odisha, and West Bengal, as well as significantly lower skeletal mass-whole body and skeletal mass-trunk. PCFA showed two components: (i) percentage body fat with muscle mass; and (ii) visceral fat with resting metabolism. These two components cumulatively explained 80-90% of the total variance associated with CVD risk variables, across the nine tribes. CONCLUSION: Tribal subjects of Gujarat had higher CVD risks with significantly higher fat mass and lower muscle mass followed by the tribal subjects of Odisha, and West Bengal respectively. The younger generation are equally at risk as their older counterparts. The CVD risks are developing at a much faster rate resulting in a serious public health threat, even in traditional societies. Body composition measures could be considered as a better non-invasive technique for early intervention and proper risk management among the Asian Indians in general and tribal populations in particular.

Influence of Zn-substitution on structural, magnetic, dielectric, and electric properties of Li-Ni-Cu ferrites.

The polycrystalline Li0.15Ni0.6-xZnxCu0.1Fe2.15O4 ferrites are fabricated by the method of conventional solid-state reaction technique. The X-ray diffraction (XRD) confirms that the structure of the composition is a single-phase cubic spinel structure for all samples. The particle size of the compositions is varied from 36 to 52 nm. The lattice parameter and densities are found to increase with enhancing Zn content, as the ionic radius and atomic weight of Zn are greater than Ni. The porosity exhibits a decreasing trend. The average grain size determined using Field Emission Scanning Microscopy (FESEM) increases until x = 0.40, then declines. The Energy-Dispersive Spectroscopy (EDS) examination revealed that the percentage of obtained elements is well matched with the stoichiometric elements. The addition of Zn content acts as an accelerator for enhancing the value of the real part of initial permeability and the highest value is obtained (µi' = 276) for the x = 0.40 sample, as well as the highest relative quality factor (RQF) of around 3000. The loss factor for the Zn substituted composition is nine times lower than for the parent composition. The optimum saturation magnetization of around 77.49 emu/g is found for the x = 0.40 sample. The maximum dielectric constant (ε' = 2.85 × 103) is found for x = 0.10 samples at 10 kHz. Further, from impedance studies, the non-Debye type dielectric relaxation is seen for the Zn-substituted samples. The observed region of the imaginary electric modulus peak signifies the transition of charge carrier mobility from a larger range to a short-range distance. The phenomenon of ac conductivity is attributed to the process of the small polaron hopping mechanism.

Astrocyte Control of Zika Infection Is Independent of Interferon Type I and Type III Expression.

Zika virus (ZIKV) is a pathogenic neurotropic virus that infects the central nervous system (CNS) and results in various neurological complications. Astrocytes are the dominant CNS cell producer of the antiviral cytokine IFN-ß, however little is known about the factors involved in their ability to mediate viral infection control. Recent studies have displayed differential responses in astrocytes to ZIKV infection, and this study sought to elucidate astrocyte cell-specific responses to ZIKV using a variety of cell models infected with either the African (MR766) or Asian (PRVABC59) ZIKV strains. Expression levels of pro-inflammatory (TNF-α and IL-1ß) and inflammatory (IL-8) cytokines following viral infection were low and mostly comparable within the ZIKV-resistant and ZIKV-susceptible astrocyte models, with better control of proinflammatory cytokines displayed in resistant astrocyte cells, synchronising with the viral infection level at specific timepoints. Astrocyte cell lines displaying ZIKV-resistance also demonstrated early upregulation of multiple antiviral genes compared with susceptible astrocytes. Interestingly, pre-stimulation of ZIKV-susceptible astrocytes with either poly(I:C) or poly(dA:dT) showed efficient protection against ZIKV compared with pre-stimulation with either recombinant IFN-ß or IFN-λ, perhaps indicating that a more diverse antiviral gene expression is necessary for astrocyte control of ZIKV, and this is driven in part through interferon-independent mechanisms.

Role of Metabolic Risk Factors, Family History, and Genetic Polymorphisms (PPARγ and TCF7L2) on Type 2 Diabetes Mellitus Risk in an Asian Indian Population.

INTRODUCTION: Women with family history of diabetes (FHD) are at significantly increased risk of developing gestational diabetes mellitus which may eventually lead to type 2 diabetes mellitus (T2DM) in later life. OBJECTIVE: This study investigates the role of FHD on metabolic markers and gene polymorphisms and hence on T2DM susceptibility in nondiabetic pregnant women and the subsequent risks in their newborns. MATERIALS AND METHODS: The present study was conducted on 200 healthy (nondiabetic and normotensive) adult Asian Indian women, including 100 with and 100 without FHD, living in and around Kolkata, India. During the gestational period, they were studied twice and followed up till delivery. During delivery, both mothers' venous blood and cord blood were collected to estimate serum CRP, glucose, and lipid profiles of the respective mothers and their newborns. Genotyping of PPARγ and TCF7L2 polymorphisms was done from these blood samples. RESULTS: A comparison of the metabolic variables among the subjects with and without FHD revealed significant differences among them. We also found close relationship between mothers and their newborn babies in terms of both PPARγ (rs1801282) C/G and TCF7L2 (rs7903146) C/T polymorphisms. More specifically, genotyping results for mothers with FHD and their newborn babies showed high concordance in inheritance of alleles: (i) for PPARγ via the risk allele G (74.0%) which is carried over to the newborn babies (64.5%) and (ii) for TCF7L2 via the risk allele T (73.0%) which is carried over to the newborn babies (68.5%). CONCLUSION: This study leads to the conclusion that Asian Indian women population based in Kolkata, India, are ethnically and genetically predisposed to the risk factors of diabetes through FHD, which is reflected in their gestational phase, and it has a significant implication on their birth outcomes.

Rural urban differences of cardiovascular disease risk factors in adult Asian Indians.

The prevalence of cardiovascular disease (CVD) risk factors in "People of Indian Origin" (PIO) is exceedingly high and strong relationships among elevated blood pressure, increased levels of lipoproteins, visceral obesity, physical inactivity and subsequent high occurrence of coronary heart disease, type 2 diabetes mellitus etc., were evident in many studies. Increasing urbanization with effective changes in lifestyles could be attributed to explain this exaggerated rate. The present community based cross-sectional investigation was aimed to identify rural-urban differences in prevalence of risk factors of CVD in the adult Asian Indians. A total of 350 adult (30 years and above) individuals (184 males and 166 females) belong to urban (n = 193, males = 104, and females = 89) and rural (n = 157, males = 80, and females = 77) areas participated in the study. Anthropometric measures, lipids profiles, fasting blood glucose and blood pressure measures were obtained from participants. The mean body mass index (kg/m2) for male and female was 22.37 +/- 4.09 and 23.20 +/- 4.37, respectively. There existed significant differences for anthropometric, metabolic, and blood pressure variables between rural and urban areas. Habitat (rural vs. urban) had significant impact on central adiposity, lipids, lipoproteins, and blood pressure measures even after adjusted for age and sex. Overall, 84.3% of females had lower HDL level compared with only 20.1% in males. It was also observed that the prevalence of metabolic syndrome was 56.2% in urban females compared with 36.4% in rural females. Effective urbanization and or modernization seem to influence CVD risk factors and warrants intervention as early as adulthood to check this menace.

Apolipoprotein E gene polymorphism and dyslipidaemia in adult Asian Indians: A population based study from Calcutta, India.

AIM: The study was aimed to determine the association of Apolipoprotein E (apo E) gene polymorphisms on lipid levels in Asian Indian population. METHODS: A total of 350 (184 males and 166 females) adult (30 years and above) Asian Indians of Calcutta and suburb participated in the study. Anthropometric measures, lipids profiles, and blood glucose measures were collected. Out of 350 subjects, a sample of 70 individuals was selected randomly for genotyping after adjusting for age and sex. The apo E gene polymorphisms were determined by agarose gel electrophoresis. RESULTS: The apo E polymorphism showed significant association with dyslipidaemia (P=0.0135) with epsilon3/4 combination has had the highest occurrence of dyslipidaemia and metabolic syndrome (MS) followed by epsilon4/4

Lipid droplet density alters the early innate immune response to viral infection.

The cellular localisation of many innate signalling events following viral infection has yet to be elucidated, however there has been a few cases in which membranes of certain cellular organelles have acted as platforms to these events. Of these, lipid droplets (LDs) have recently been identified as signalling platforms for innate TLR7 and 9 signalling. Despite their wide range of similar roles in various metabolic pathways, LDs have been overlooked as potential platforms for antiviral innate signalling events. This study established an in vitro model to evaluate the efficiency of the early innate immune response in cells with reduced LD content to the viral mimics, dsDNA and dsRNA, and Sendai viral infection. Using RT-qPCR, the expression of IFN-ß and IFN-λ was quantified following stimulation along with the expression of specific ISGs. Luciferase based assays evaluated the combined expression of ISRE-promoter driven ISGs under IFN-ß stimulation. Cellular LD content did not alter the entry of fluorescently labelled viral mimics into cells, but significantly decreased the ability of both Huh-7 and HeLa cells to produce type I and III IFN, as well as downstream ISG expression, indicative of an impeded innate immune response. This observation was also seen during Sendai virus infection of HeLa cells, where both control and LD reduced cells replicated the virus to the same level, but a significantly impaired type I and III IFN response was observed in the LD reduced cells. In addition to altered IFN production, cells with reduced LD content exhibited decreased expression of specific antiviral ISGs: Viperin, IFIT-1 and OAS-1 under IFN-ß stimulation; However the overall induction of the ISRE-promoter was not effected. This study implicates a role for LDs in an efficient early innate host response to viral infection and future work will endeavour to determine the precise role these important organelles play in induction of an antiviral response.

High prevalence of metabolic syndrome and its correlates in two tribal populations of India and the impact of urbanization.

BACKGROUND AND OBJECTIVES: Metabolic syndrome is one of the major causes of morbidity and mortality in the world. The prevalence of this syndrome is high among Asians, including Indians, and is rising, particularly with the adoption of a modernized life style. Whether traditional societies in India have a low prevalence and the extent to which a transition to a modern life style contributes to the increase in prevalence are unknown. To examine the role of environmental and genetic factors in metabolic syndrome we conducted a study in two sub-Himalayan tribal populations with shared ancestry (Toto and Bhutia). The Toto live exclusively in a rural area, whereas a section of the Bhutia has adopted a modern life style. METHODS: Fasting (12 h) blood samples of Toto (n=258); rural Bhutia (n=75) and urban Bhutia (n=230) were collected, with written informed consent. Lipid profile, blood pressures, body fat and other anthropometric parameters were assessed. Criteria suggested by National Cholesterol Education Programme (NCEP) Adult Treatment Panel III (2001) were used for assessment of metabolic syndrome. RESULTS: The prevalence of metabolic syndrome was high (about 30-50%) among the Bhutia, with no significant rural-urban difference. Among the Toto, though the prevalence of metabolic syndrome was low (about 4-9%), their lipid levels were alarmingly adverse (about 37-67% had low HDLcholesterol or high triglyceride levels). There was an additional adverse impact of adoption of urban life-styles (perhaps primarily mediated through dietary changes) on cardiovascular risk factors. INTERPRETATION AND CONCLUSION: Our study suggested that metabolic syndrome and its correlates could be a major health problem even in traditional societies, indicating that this syndrome was not necessarily a result of modernization. Further, our study indicates that genetic factors that adversely affect the levels of such variables have long antiquities in Indian ethnic groups.

Presence of high rates of overweight and obesity among adult Marwaris of Howrah, West Bengal, India.

A cross-sectional study of 220 (110 men and 110 women) adult (> 20 years) Marwaris of Howrah, West Bengal, India, was undertaken to investigate the frequency of overweight and obesity, using different criteria. Results revealed that men had significantly greater mean height, weight, waist circumference (WC), waist-hip ratio (WHR), conicity index (CI) and fat free mass (FFM), compared with women. Women had significantly higher mean body mass index (BMI), biceps (BSF) and triceps (TSF) skinfolds, mid-upper arm (MUAC) and hip (HC) circumferences, percent body fat (PBF), fat mass index (FMI), mid-arm fat area (MAFA) and PBF/BMI ratio compared with men. The frequency of overweight (BMI > or = 25.0) was significantly higher among women (71.8%) compared with men (44.5%). Similarly, significantly more women (41.8%) had high WHR than men (22.7%). Significantly more women also had high PBF (97.3%) compared with men (90.9%). In conclusion, these results demonstrated that the level of overall and central adiposity, as well as body fat, was found to be high among Marwaris, as compared with other ethnic populations of India. Moreover, there existed significant sexual dimorphism in these measures among this ethnic group. This high level of overall and central adiposity and body fat could have severe adverse health implications in this ethnic group.

Association of DNA Methylation at CPT1A Locus with Metabolic Syndrome in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) Study.

In this study, we conducted an epigenome-wide association study of metabolic syndrome (MetS) among 846 participants of European descent in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN). DNA was isolated from CD4+ T cells and methylation at ~470,000 cytosine-phosphate-guanine dinucleotide (CpG) pairs was assayed using the Illumina Infinium HumanMethylation450 BeadChip. We modeled the percentage methylation at individual CpGs as a function of MetS using linear mixed models. A Bonferroni-corrected P-value of 1.1 x 10(-7) was considered significant. Methylation at two CpG sites in CPT1A on chromosome 11 was significantly associated with MetS (P for cg00574958 = 2.6x10(-14) and P for cg17058475 = 1.2x10(-9)). Significant associations were replicated in both European and African ancestry participants of the Bogalusa Heart Study. Our findings suggest that methylation in CPT1A is a promising epigenetic marker for MetS risk which could become useful as a treatment target in the future.

Rhinovirus Load Is High despite Preserved Interferon-ß Response in Cystic Fibrosis Bronchial Epithelial Cells.

Lung disease in cystic fibrosis (CF) is often exacerbated following acute upper respiratory tract infections caused by the human rhinovirus (HRV). Pathophysiology of these exacerbations is presently unclear and may involve deficient innate antiviral or exaggerated inflammatory responses in CF airway epithelial cells. Furthermore, responses of CF cells to HRV may be adversely affected by pre-exposure to virulence factors of Pseudomonas (P.) aeruginosa, the microorganism that frequently colonizes CF airways. Here we examined production of antiviral cytokine interferon-ß and inflammatory chemokine interleukin-8, expression of the interferon-responsive antiviral gene 2'-5'-oligoadenylate synthetase 1 (OAS1), and intracellular virus RNA load in primary CF (delF508 CFTR) and healthy airway epithelial cells following inoculation with HRV16. Parallel cells were exposed to virulence factors of P. aeruginosa prior to and during HRV16 inoculation. CF cells exhibited production of interferon-ß and interleukin-8, and expression of OAS1 at levels comparable to those in healthy cells, yet significantly higher HRV16 RNA load during early hours post-inoculation with HRV16. In line with this, HRV16 RNA load was higher in the CFBE41o- dF cell line overexpessing delF508 CFTR, compared with the isogenic control CFBE41o- WT (wild-type CFTR). Pre-exposure to virulence factors of P. aeruginosa did not affect OAS1 expression or HRV16 RNA load, but potentiated interleukin-8 production. In conclusion, CF cells demonstrate elevated HRV RNA load despite preserved interferon-ß and OAS1 responses. High HRV load in CF airway epithelial cells appears to be due to deficiencies manifesting early during HRV infection, and may not be related to interferon-ß.

Lipid changes due to fenofibrate treatment are not associated with changes in DNA methylation patterns in the GOLDN study.

Fenofibrate lowers triglycerides (TG) and raises high density lipoprotein cholesterol (HDLc) in dyslipidemic individuals. Several studies have shown genetic variability in lipid responses to fenofibrate treatment. It is, however, not known whether epigenetic patterns are also correlated with the changes in lipids due to fenofibrate treatment. The present study was therefore undertaken to examine the changes in DNA methylation among the participants of Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. A total of 443 individuals were studied for epigenome-wide changes in DNA methylation, assessed using the Illumina Infinium HumanMethylation450 array, before and after a 3-week daily treatment with 160 mg of fenofibrate. The association between the change in DNA methylation and changes in TG, HDLc, and low-density lipoprotein cholesterol (LDLc) were assessed using linear mixed models adjusted for age, sex, baseline lipids, and study center as fixed effects and family as a random effect. Changes in DNA methylation were not significantly associated with changes in TG, HDLc, or LDLc after 3 weeks of fenofibrate for any CpG. CpG changes in genes known to be involved in fenofibrate response, e.g., PPAR-α, APOA1, LPL, APOA5, APOC3, CETP, and APOB, also did not show evidence of association. In conclusion, changes in lipids in response to 3-week treatment with fenofibrate were not associated with changes in DNA methylation. Studies of longer duration may be required to detect treatment-induced changes in methylation.

Novel tandem synthesis of bis(µ-NN'-tetrazolate) bridged dinuclear nickel(ii) Schiff base complex via [3 + 2] cyclo-addition at ambient condition.

A novel bis(µ-NN'-tetrazolate) bridged centrosymmetric dinuclear nickel(ii) Schiff base complex [Ni2(L)2(PTZ)2]·2H2O·2CH3CN (HL is a tridentate Schiff base, 2-((2-(ethylamino)ethylimino)methyl)-6-methoxyphenol and HPTZ is 5-pyrazinyltetrazole) has been synthesized via [3 + 2] cyclo-addition reaction of 2-cyanopyrazine and sodium azide in presence of nickel(ii) acetate tetrahydrate and HL. The structure of the complex is confirmed by single crystal X-ray diffraction analysis. The combination of H-bonding and C-Hπ interactions creates a 3(6)-hxl topological supramolecular network. The acetonitrile molecules are encapsulated as a hydrophobic guest within the 2D supramolecular network.

Formation of bis(µ-tetrazolato)dinickel(II) complexes with N,N,O-donor Schiff bases via in situ 1,3-dipolar cyclo-additions: isolation of a novel bi-cyclic trinuclear nickel(II)-sodium(I)-nickel(II) complex.

A dinuclear and a novel bi-cyclic hetero trinuclear bis(µ-tetrazolato) bridged nickel(II) Schiff base complexes [Ni2(L(1))2(PTZ)2] (1) and [Ni2(L(2))2(PTZ)2Na(H2O)]ClO4·H2O (2) {where HL(1) = 2-((2-(dimethylamino)ethylimino)methyl)-6-methoxyphenol, HL(2) = 2-((2-(methylamino)ethylimino)methyl)-6-methoxyphenol and HPTZ = 5-(2-pyridyl)tetrazole} have been synthesized by in situ 1,3-dipolar cyclo-addition and characterized by spectral analysis, X-ray crystallography, and variable-temperature magnetic susceptibility measurements. Both the complexes crystallize in monoclinic space group P2(1)/c. Both the complexes feature double µ-NN'-tetrazolato bridged dinickel(II) structures, in which each nickel(II) is coordinated meridionally by a depronated terdentate Schiff base [(L(1))(-) for 1 and (L(2))(-) for 2] and two nitrogen atoms of the (PTZ)(-). A nitrogen atom from a symmetry related bridging (PTZ)(-) coordinates to complete the distorted octahedral geometry of nickel(II). The phenoxo and methoxo oxygen atoms from two [NiL(2)] units and a water molecule coordinate to a sodium(I) to form the unique bi-cyclic trinuclear nickel(II)-sodium(I)-nickel(II) core in complex 2. Very strong π···π stacking is observed in complex 2 to form a supramolecular chain. The variable-temperature (1.8-300 K) magnetic susceptibility measurements show the presence of anti-ferromagnetic coupling between two nickel(II) centers for both complexes with J = -2.14(1) cm(-1) (for 1) and J = -1.20(2) cm(-1) (for 2). To obtain a better understanding of the magnetic exchange mechanism, quantum mechanical (DFT) calculations have been performed. The calculated J values [J(theo) = -4.53 cm(-1) (for 1) and J(theo) = -2.48 cm(-1) (for 2)] are in agreement with the values obtained experimentally.

Synergistic effects of ACE (I/D) and Apo E (Hha I) gene polymorphisms on obesity, fat mass, and blood glucose level among the adult Asian Indians: A population-based study from Calcutta, India.

The study was aimed to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) and apolipoprotein E (Apo E) Hha I gene polymorphisms with obesity, fat mass, and blood glucose levels in Asian Indian population. A total of 350 (184 men and 166 women) adult (30 years and above) Asian Indians of Calcutta and suburb participated in the study. Anthropometric measures, fat mass, and blood glucose measures were collected. Out of 350 subjects, a sample of 139 individuals was collected randomly for genotyping (adjusted for age and sex). The ACE and Apo E genotypes were determined by agarose gel electrophoresis. It was observed that neither ACE (I/D) nor Apo E (Hha I) gene polymorphisms showed any significant association with body mass index, waist circumference, fat mass, fasting, and post meal blood glucose levels. Even synergistically (ACE + Apo E), these two polymorphisms showed no significant association with obesity, fat mass, and blood glucose level. ACE (I/D), Apo E (Hha I), as well as ACE + Apo E seem to have no significant association with obesity, fat mass, and blood glucose levels in this population.

Family history of type 2 diabetes and prevalence of metabolic syndrome in adult Asian Indians.

BACKGROUND: Our objective was to test the association between familial risk of type 2 diabetes mellitus (T2DM) and the prevalence of metabolic syndrome (MS) in adult Asian Indians. MATERIALS AND METHODS: A total of 448 adult (>30 years) individuals (257 males and 191 females) participated in the study. Familial risk of T2DM was classified into three groups viz., 1=both parents affected; 2=parent and/or siblings affected and 3=none or no family history for T2DM. Anthropometric measures, blood pressures, fasting blood glucose and metabolic profiles were studied using standard techniques. MS was defined accordingly. The prevalence of MS phenotypes was estimated and compared among the three familial risk strata. RESULTS: Individuals with a history of both parents affected from diabetes had significantly higher (P<0.001) body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting blood glucose (FBG; P=0.035) than individuals having no family history of T2DM. Significant difference was also noticed between individuals with and without MS according to the family history of diabetes (P<0.001). Differences were evident between individuals who fulfilled all the MS criteria (P=0.001) and individuals with only one or two criteria (phenotypes) according to family history of T2DM. CONCLUSION: Family history of T2DM had significant effect on individuals with MS as compared to their counterparts (individuals having no family history of T2DM). It therefore seems reasonable to argue that family history of T2DM could be useful as a predictive tool for early diagnosis and prevention of MS in Asian Indian population.

Prevalence of cardiovascular disease risk factors by habitat: a study on adult Asian Indians in West Bengal, India.

The present community based cross-sectional study was aimed to investigate whether or not increasing prevalence of cardiovascular disease (CVD) risk factors in adult Asian Indian population are associated with increasing urbanization. The 'urban group' was comprised of 224 individuals including 122 males and 102 females being inhabitants of Kolkata (erstwhile Calcutta) under the Kolkata Metropolitan Development Authority (KMDA) area. The 'rural group' comprised 224 individuals including 135 males and 89 females and was living in a village council located about 80 kilometers from Kolkata. Therefore, a total of 448 adult (> or = 30 years) individuals (257 males and 191 females) participated in the study. Anthropometric measures, lipids profiles, fasting blood glucose and blood pressure measures were taken from participants. Obesity and body composition measures were subsequently calculated from the anthropometric measures. Accepted cut-offs were used to define metabolic syndrome (MS), lipids abnormalities, increased adiposity and high blood pressure in the study. It was found that 58.7% participants were engaged in sedentary work which includes 60.7% males and 56% females. It was further observed that the prevalence of high blood pressure was as high as 70.6% in urban females compared to 55.1% in rural females. However, the prevalence of low HDLc was remarkably high in females ofboth rural and urban areas. The prevalence ofMS was significantly higher in urban females (57.8%) than in their rural counterparts (34.8%). It seems reasonable to argue that people with changing lifestyles due to growing urbanization are associated with adverse CVD risk factors irrespective of their habitat (rural vs. urban). This in turn warranted a comprehensive risk stratification protocol at the national level for the effective management of CVD risk factors in this part of the world.

Factor analysis of risk variables associated with metabolic syndrome in adult Asian Indians.

BACKGROUND: Several studies hinted about the clustering of risk variables of the metabolic syndrome (MS) and suggested that the underlying genetic polymorphisms could be responsible for the increasing incidence of coronary heart disease (CHD) in people of Indian origin. Therefore, identification of the components of the MS along with the genetic factors could be one of the aspects to make an attempt to prevent the increasing incidence of CHD. MATERIALS AND METHODS: Principal component factor analysis (PCFA) was undertaken to identify the components or factors of the MS among the adult (≥30 years) Asian Indians living in and around Calcutta, India. The study comprised 350 adult Asian Indians. Anthropometric measurements were taken, and lipid profiles, blood pressure and fasting blood glucose were measured for each participant. Two genetic polymorphisms, namely, angiotensin converting enzyme (ACE) gene polymorphism (insertion/deletion [I/D]) or ACE (I/D) and apolipoproteinE (Hha I) were also studied. RESULTS: PCFA revealed 3 factors that cumulatively explained 65.39% of the observed variance of the MS by measured variables. The 3 factors identified were lipids and lipoprotein (Factor 1), centripetal fat and blood pressure (Factor 2), and ACE (I/D) polymorphism with blood pressure (Factor 3). Moreover, the first 2 factors, that is, lipids, lipoprotein, centripetal fat, and blood pressures cumulatively explained ~46% (45.94%) of the observed variance of MS in this population. CONCLUSIONS: Since more than 1 factor was identified for the MS phenotype, more than 1 physiogenetic mechanism could be accounted for MS in the Asian Indian population.

Association of metabolic syndrome with obesity measures, metabolic profiles, and intake of dietary fatty acids in people of Asian Indian origin.

OBJECTIVE: The present community-based cross-sectional study was aimed to examine the association of metabolic syndrome (MS) with obesity measures, metabolic profiles, and intake of dietary fatty acids in Asian Indian population. PATIENTS AND METHODS: A total of 350 adult (30 years and above) individuals (184 males and 166 females) inhabiting in and around Kolkata, India participated in this study. MS was defined using the protocol specifically designed for Asian Indian population. RESULTS: The prevalence of MS in the study was 31.4%. The prevalence was significantly higher (P < 0.01) in females (48.2%) as compared to males (16.3%). It was observed that males without MS had significantly higher mean waist circumference (WC P < 0.05); waist-hip ratio (WHR; P < 0.001); triglyceride (TG; P < 0.05); very low density lipoprotein cholesterol (VLDLc; P < 0.05) and fasting blood glucose (FBG; P < 0.01) as compared to females without MS. Significant differences were also observed for dietary intake of total fatty acids (TFA; P < 0.001); saturated fatty acids (SFA; P < 0.001) and polyunsaturated fatty acids (PUFA; P < 0.001) between individuals with and without MS. However, no significant association was observed in individuals with MS after controlling for age and sex. On the other, WC and body mass index (BMI) had significant correlation with SFA: mono unsaturated fatty acids (MUFA; P < 0.01) in individuals without MS even after controlling for age and sex. CONCLUSION: It seem reasonable to argue that while dealing with MS in Asian Indians, clinicians should consider obesity measures, metabolic profiles and dietary fatty acids simultaneously.