Laryngotracheal stenosis: clinical profile, surgical management and outcome.

Despite the availability of various surgical options, management of laryngotracheal stenosis (LTS) still remains an enigma. Proper selection of surgical technique in each clinical setting is the key for successful outcome. The purpose of this article is to guide one in selection of appropriate surgical procedures depending upon various stenosis parameters. Aim To record the clinical profile of cases with LTS. To assess the outcome following various surgical interventions based on site, severity, cause of stenosis and to derive conclusions regarding treatment options in various stenosis. Materials and Methods It is a study of 60 cases with chronic LTS. It includes retrospective study of 30 cases treated from 2004 and prospective study of 30 cases from Jan 2007 to Dec 2009. A total of 60 cases with LTS were enrolled in the study. Patients were assessed clinically by eliciting detailed history and analyzing previous records. After assessment of extent of stenosis, they were subjected to surgical interventions (endoscopic/open approach). Outcome after surgical interventions was assessed. Results 60 patients were included in the study, in the age group of 2.5-50 years. There were 46 (77%) male patients and 14 (23%) female patients. Intrinsic trauma, secondary to prolonged intubation was the most common cause of LTS, seen in 23 (38%) cases followed by post traumatic stenosis (strangulation-18 (30%), blunt injury-15 (25%), penetrating neck injury-4 (7%)). Stenosis was divided into 6 types based on subsite involvement. Of which, cervical trachea was the commonest site of involvement (25/60 cases). Majority of cases had fixed vocal cords at presentation (55%), more commonly due to post traumatic injury. 60 cases had undergone a total of 110 surgical procedures (endoscopic-56,open approach-54). In the end, overall decannulation rate is 93.3%. In site wise tracheal stenosis, isolated subglottis, combined glottis and subglottic stenosis had decannulation rate of 100% each and with mobile vocal cords, the success rate is 96%. Conclusions Post traumatic stenosis with fixed vocal cords is more common in our practice. Categorizing stenosis into various subtypes helps in treatment planning and predicts surgical outcome. Tracheal or subglottic stenosis with mobile vocal cords has better success rate.

INSIG2 variants, dietary patterns and metabolic risk in Samoa.

BACKGROUND/OBJECTIVES: Association of insulin-induced gene 2 (INSIG2) variants with obesity has been confirmed in several but not all follow-up studies. Differences in environmental factors across populations may mask some genetic associations and therefore gene-environment interactions should be explored. We hypothesized that the association between dietary patterns and components of the metabolic syndrome could be modified by INSIG2 variants. SUBJECTS/METHODS: We conducted a longitudinal study of adiposity and cardiovascular disease risk among 427 and 290 adults from Samoa and American Samoa (1990-1995). Principal component analysis on food items from a validated food frequency questionnaire was used to identify neotraditional and modern dietary patterns. We explored gene-dietary pattern interactions with the INSIG2 variants rs9308762 and rs7566605. RESULTS: Results for American Samoans were mostly nonsignificant. In Samoa, the neotraditional dietary pattern was associated with lower triglycerides, body mass index (BMI), waist circumference, systolic and diastolic blood pressure and fasting glucose (all P-for-trend<0.05). The modern pattern was significantly associated with higher triglycerides, BMI, waist circumference and lower high-density lipoprotein-cholesterol (all P-for-trend<0.05). A significant interaction for triglycerides was found between the modern pattern and the rs9308762 polymorphism (P=0.04). Those from Samoa consuming the modern pattern have higher triglycerides if they are homozygous for the rs9308762 C allele. CONCLUSIONS: The common INSIG2 variant rs9308762 was associated with poorer metabolic control and a greater sensitivity of trigylcerides to a modern dietary pattern. Environmental factors need to be taken into account when assessing genetic associations across and within populations.

Fatty Acid desaturase gene variants, cardiovascular risk factors, and myocardial infarction in the costa rica study.

Genetic variation in fatty acid desaturases (FADS) has previously been linked to long-chain polyunsaturated fatty acids (PUFAs) in adipose tissue and cardiovascular risk. The goal of our study was to test associations between six common FADS polymorphisms (rs174556, rs3834458, rs174570, rs2524299, rs174589, rs174627), intermediate cardiovascular risk factors, and non-fatal myocardial infarction (MI) in a matched population based case-control study of Costa Rican adults (n = 1756). Generalized linear models and multiple conditional logistic regression models were used to assess the associations of interest. Analyses involving intermediate cardiovascular risk factors and MI were also conducted in two replication cohorts, The Nurses' Health Study (n = 1200) and The Health Professionals Follow-Up Study (n = 1295). In the Costa Rica Study, genetic variation in the FADS cluster was associated with a robust linear decrease in adipose gamma-linolenic, arachidonic, and eicosapentaenoic fatty acids, and significant or borderline significant increases in the eicosadienoic, eicosatrienoic, and dihomo-gamma-linolenic fatty acids. However, the associations with adipose tissue fatty acids did not translate into changes in inflammatory biomarkers, blood lipids, or the risk of MI in the discovery or the replication cohorts. In conclusion, fatty acid desaturase polymorphisms impact long-chain PUFA biosynthesis, but their overall effect on cardiovascular health likely involves multiple pathways and merits further investigation.

Genetic variation in fatty acid elongases is not associated with intermediate cardiovascular phenotypes or myocardial infarction.

BACKGROUND/OBJECTIVES: Elongases 2, 4 and 5, encoded by genes ELOVL2, ELOVL4 and ELOVL5, have a key role in the biosynthesis of very long chain polyunsaturated fatty acids (PUFAs). To date, few studies have investigated the associations between elongase polymorphisms and cardiovascular health. We investigated whether ELOVL polymorphisms are associated with adipose tissue fatty acids, serum lipids, inflammation and ultimately with nonfatal myocardial infarction (MI) in a Costa Rican population. SUBJECTS/METHODS: MI cases (n=1650) were matched to population-based controls (n=1650) on age, sex and area of residence. Generalized linear and multiple conditional logistic regression models were used to assess the associations between seven common ELOVL polymorphisms and cardiometabolic outcomes. Analyses were replicated in The Nurses' Health Study (n=1200) and The Health Professionals Follow-Up Study (n=1295). RESULTS: Variation in ELOVL2, ELOVL4 and ELOVL5 was not associated with adipose tissue fatty acids, intermediate cardiovascular risk factors or MI. In the Costa Rica study, the number of the minor allele copies at rs2294867, located in the ELOVL5 gene, was associated with an increase in total and LDL cholesterol (adjusted P-values=0.001 and <0.0001 respectively). Additionally, the number of the minor allele copies at rs761179, also located in the ELOVL5 gene, was significantly associated with an increase in total cholesterol (adjusted P-value=0.04). However, the observed associations were not replicated in independent populations. CONCLUSION: Common genetic variants in elongases are not associated with adipose tissue fatty acids, serum lipids, biomarkers of systemic inflammation, or the risk of MI.

Prevalence of metabolic syndrome and related metabolic traits in an island population of the Adriatic.

BACKGROUND: Metabolic syndrome, a constellation of risk factors associated with cardiovascular disease and Type 2 diabetes, has reached epidemic proportions worldwide. Epidemiological studies in transitional societies will provide insight into the underlying factors that interact in its manifestation. AIMS: To estimate the prevalence of metabolic syndrome, provide a comparative analysis of two metabolic syndrome definitions and assess clustering and association of metabolic traits and cardiovascular diseases in an Adriatic island population. SUBJECTS AND METHODS: In a cross-sectional study, data on four anthropometric, blood pressure and 11 biochemical traits were obtained from 1430 adults from the island of Hvar. RESULTS: Prevalence of metabolic syndrome was 25% and 38.5% based on Adult Treatment Panel III and International Diabetes Federation definitions, respectively. Rates of abdominal obesity, elevated blood glucose and hypertension were high. Among the traits not included in the definitions, levels of LDL, total cholesterol and fibrinogen were markedly elevated. The majority of the phenotypes were significantly associated with the syndrome, the strongest being waist circumference. CONCLUSION: The Croatian islanders are characterized by a high prevalence of metabolic abnormalities. Central obesity is the strongest contributor of the syndrome. With a high prevalence of dyslipidemia and pro-inflammatory factors, the population is at substantial risk for cardiovascular diseases.

Smoking and family history and risk of aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Smoking and family history of aneurysmal subarachnoid hemorrhage (aSAH) are independent risk factors for aSAH. Using a population-based case-control study of hemorrhagic stroke, we hypothesized that having both a first-degree relative with a brain aneurysm or SAH (+FH) and current smoking interact to increase the risk of aSAH. METHODS: Cases of aneurysmal SAH were prospectively recruited from all 17 hospitals in the five-county region around the University of Cincinnati. Controls were identified by random digit dialing. Controls were matched to cases of aSAH by age (+/-5 years), race, and sex. Conditional multiple logistic regression was used to identify independent risk factors. For deviation from the additive model, the interaction constant ratio test was used. RESULTS: A total of 339 cases of aSAH were matched to 1,016 controls. Compared to current nonsmokers with no first-degree relatives with aSAH (-FH), the odds ratio (OR) for aSAH for current nonsmokers with +FH was 2.5 (95% confidence interval [CI] 0.9-6.9); for current smokers with -FH, OR = 3.1 (95% CI 2.2-4.4); and for current smokers with +FH, OR = 6.4 (95% CI 3.1-13. 2). The interaction constant ratio, which measured the deviation from the additive model, was significant: 2.19 (95% CI 0.80-5.99). The lower bound of the 95% CI >0.5 signifies a departure from the additive model. CONCLUSION: Evidence of a gene-environment interaction with smoking exists for aneurysmal subarachnoid hemorrhage. This finding is important to counseling family members and for screening of intracranial aneurysm (IA) as well as the design and interpretation of genetic epidemiology of IA studies.

A whole genome linkage scan identifies multiple chromosomal regions influencing adiposity-related traits among Samoans.

We conducted a genome-wide scan in 46 pedigrees, with 671 phenotyped adults, from the independent nation of Samoa to map quantitative trait loci (QTLs) for adiposity-related phenotypes, including body mass index (BMI), abdominal circumference (ABDCIR), percent body fat (%BFAT), and fasting serum leptin and adiponectin. A set of 378 autosomal and 14 X chromosomal microsatellite markers were genotyped in 572 of the adults. Significant genetic correlations (0.82-0.96) were detected between pairs of BMI, ABDCIR, %BFAT and leptin. Suggestive linkages were found on 13q31 (LOD = 2.30 for leptin, LOD = 2.48 for %BFAT, LOD = 2.04 for ABDCIR, and LOD = 2.09 for BMI) and on 9p22 (LOD = 3.08 for ABDCIR and LOD = 2.53 for %BFAT). Furthermore, bivariate linkage analyses indicated that the genetic regions on 9p22 (bivariate LOD 2.35-3.10, LOD(eq) (1df) 1.88-2.59) and 13q31 (bivariate LOD 1.96-2.64, LOD(eq) 1.52-2.21) might harbor common major genes with pleiotropic effects. Other regions showing suggestive linkage included 4q22 (LOD = 2.95) and 7p14 (LOD = 2.64) for %BFAT, 2q13 for adiponectin (LOD = 2.05) and 19q12 for BMI-adjusted leptin (LOD = 2.03). Further fine mapping of these regions may help identify the genetic variants contributing to the development of obesity in Samoan adults.

Genome-wide scan for adiposity-related phenotypes in adults from American Samoa.

OBJECTIVE: To detect quantitative trait loci influencing adiposity-related phenotypes assessed by body mass index (BMI), abdominal circumference (ABDCIR), percent body fat (%BFAT) and fasting serum leptin and adiponectin using a whole genome linkage scan of families from American Samoa. DESIGN: Family-based linkage analysis, the probands and family members were unselected for obesity. SUBJECTS: A total of 583 phenotyped American Samoan adults, of which 578 were genotyped in 34 pedigrees. MEASUREMENTS: A total of 377 autosomal and 18 X chromosome microsatellite markers were typed at an approximate average spacing of 10 cM spanning the genome. Multipoint LOD (logarithm of the odds) scores were calculated using variance-components approaches and SOLAR/LOKI software. The covariates simultaneously evaluated were age, sex, education, farm work and cigarette smoking, with a significance level of 0.1. Due to the stochastic nature of LOKI, we report the average of maximum LOD scores from 10 runs. RESULTS: Significant linkage to leptin was found at 6q32.2 with LOD of 3.83. Suggestive linkage to leptin was found at 16q21:LOD=2.98, 1q42.2:LOD=1.97, 5q11.2:LOD=2.08, 12q24.23:LOD=2.00, 19p13.3:LOD=2.05; adiponectin was linked to 13q33.1-q22.1:LOD=2.41; %BFAT was linked to 16q12.2-q21, LOD=2.24; ABDCIR was linked to 16q23.1:LOD=1.95; %BFAT-adjusted leptin to 14q12, LOD=2.01; %BFAT-adjusted ABDCIR to 1q31.1, LOD=2.36, to 3q27.3-q28, LOD=2.10 and to 12p12.3, LOD=2.04. CONCLUSION: We found strong evidence for a major locus on 6q23.2 influencing serum leptin levels in American Samoans. The 16q21 region appears to harbor a susceptibility locus that has significant pleiotrophic effects on phenotypes BMI, %BFAT, leptin and ABDCIR as shown by bivariate linkage analyses. Several other loci of varying significance were detected across the genome.

Functional assessment of immune markers of graft rejection: a comprehensive study in live-related donor renal transplantation.

A better understanding of the immunobiological processes and predictors of graft rejection holds promise for the development of potential therapeutic strategies and also individualization of immunosuppression. The objective of this study is to analyze the clinical relevance of immune parameters such as antidonor antihuman leukocyte antigen (anti-HLA) antibodies, monitoring of cytokines and their receptors on the graft outcome following live-related donor renal transplantation. Flow cytometry-based methods were used to detect antidonor antibodies (flow cytometry crossmatch, FCXM) and intracellular cytokines. Enzyme-linked immunosorbent assay (ELISA) methods were employed to detect anti-HLA class I and class II antibodies and quantitative serum-soluble interleukin-2 receptor (sIL-2R) levels. The data revealed that patients with HLA class I-specific IgG antibody experienced higher acute rejection (AR) episodes at 1 yr in comparison to the antibody negative group (82% vs. 56%, p = 0.01). On the contrary, donor-specific class II antibodies (B+) did not have any influence on the graft survival. However, 15 recipients having both T- and B-cell antidonor antibodies (T+B+) had significantly poor graft survival (60%) as compared to the antibody-negative group (T-B-, 82%, p = 0.05). Additionally, patients having non-donor but HLA-specific antibodies (FCXM-/ELISA+) had poor graft survival as compared to the antibody-negative group (64% vs. 88%, p < 0.05). Further, patients undergoing AR episodes had significantly higher expression of IFN-gamma-producing T cells (19.16 +/- 7.4% median 17.50) as compared to their pre-transplant levels (5.68 +/- 1.63%, Median 5.20) and the non-rejecter group (5.97 +/- 4.39%, median 4.3, p = 0.0004). Similarly sIL-2 was significantly increased in AR episodes during the first month of transplantation (292 +/- 131.5 pmol/L) as compared to those with well-functioning grafts (p = 0.01) and healthy controls (p = 0.001). Evaluation of antidonor antibodies by flow cytometry is found to be relatively more sensitive and a better predictor of graft outcome. Further monitoring of cytokine expression profile of primed peripheral T-helper cells and quantitative analysis of sIL-2R offer additional valuable diagnostic and prognostic tools for follow-up of transplant subjects and a better alternative for functional assessment of immunosuppression.

Variability in TRBV haplotype frequency and composition in Caucasian, African American, Western African and Chinese populations.

The polymorphic T-cell receptor Vbeta (TRBV) genes encode much of the variable region of the T-cell receptor beta chain. Analysis of allele frequencies of three closely linked polymorphic TRBV genes, TRBV7-3, TRBV9 and TRBV6-4, was undertaken in several populations. The frequencies of these alleles are not significantly different in populations of Caucasians, African Americans and Western Africans. However, Chinese population is extremely homogenous at all three loci. The current study identifies the existence of haplotypic relationships between alleles of these genes in the Caucasian population. The ORF allele TRBV7-3*A3 is found exclusively on chromosomes bearing TRBV9*A2 and TRBV6-4*A2 in this cohort. In contrast, TRBV7-3*A1 and the null allele TRBV7-3*A2 are associated only with TRBV9*A1 and TRBV6-4*A1. This pattern of linkage disequilibrium (LD) is altered in the African American and Western African populations. In these cohorts, there is a marked reduction in LD between alleles of TRBV7-3 and TRBV9. This study is consistent with previous population genetic studies wherein African-derived samples have a greater level of genetic diversity compared to Caucasians. These data also demonstrate that patterns of LD are not consistent across the entire TRBV locus.

TGFBR1*6A is not associated with prostate cancer in men of European ancestry.

The TGFBR1*6A (*6A) variant in exon 1 of the TGFBR1 gene has been postulated as a putative tumor susceptibility allele in several studies. We have performed a case-control study in 537 men with histologically verified prostate cancer and in 488 unrelated controls to investigate the association of *6A with prostate cancer. Our results revealed that the frequency of the (*)6A allele does not differ in men with prostate cancer compared to healthy controls, even in a subset of age-matched cases and controls. There is no compelling evidence for an association of the *6A variant with prostate cancer.

Immunological monitoring of posttransplant allograft sensitization following living related donor renal transplantation.

A better understanding of the immunobiological processes and predictors of graft rejection holds promise for development of new therapeutic strategies and also for individualization of immunosuppression. The objective of this study was to analyze the clinical relevance of immune parameters, such as recipient sensitization status, donor-specific antibodies, and anti-HLA antibodies, which are major predictors of graft outcome following renal transplantation. Sera from 264 renal recipients at different posttransplant period were included for detection of anti-donor antibodies (by flowcytometry); anti-HLA, antibody (by ELISA), and panel-reactive antibodies (PRA) by complement-dependent cytotoxicity (CDC) methods. Graft survival was analyzed in relation to posttransplant PRA at 2 years follow-up time: overall survival was significantly compromised in the highly sensitized group (group III) compared to the other two groups (overall chi2 = 24.20, P = 5.5 x 10(-06)). Flow cytometric cross-matches revealed the presence of anti-donor class I antibodies (T+) in 39 patients who had a poor graft survival of 51% compared with 85% survival in 225 antibody-negative patients. (chi2 = 22.260, P = 2.381 x 10(-.06)). Further analysis was performed based on the presence or absence of FCXM and ELISA-detected antibodies. Recipients belonging to group I (ELISA+/FCXM+) showed significantly lower graft survival (43%) compared with that observed in group II, which were essentially nonsensitized individuals (90%; P = 3.1 x 10(-08)). The graft survival in the ELISA-/FCXM+ group was 63%, which was significantly lower than that in group II (P = 5.14 x 10(-03)). Group IV (ELISA+/FCXM-) including 38 (14%) serum samples with nondonor but HLA-specific antibodies was associated with significantly poorer graft survival (63%) compared with group II (P = 6.6 x 10(-05)). Our data also show that while FCXM is the most sensitive test to detect donor-specific antibodies, the ELISA method offers the additional advantage of detecting anti-HLA class-I antibodies, which are detrimental for renal graft survival. Thus the use of multiple parameters to assess recipient immune profile can predict graft outcome more accurately thus helping the individualization and optimization of immunosuppression.

Osteoma of the paranasal sinuses.

Osteamas of the paranasal sinuses are rare, They often appear as a coincidental finding on X-ray in patients having radiographs for same other reasons. Tomographic evaluation is the mainstay surgical access and its subsequent follow up. We report a series of 20 cases of osteamas of the paranasal sinuses who underwent surgery for their symptoms. Wide exposure at surgery is necessary for complete or near complete removal. Tumour close to the dura, optic-nerve and internal carotid artery may be left Close and long period offollow-up is essential, especially when the tumour is partially left behind. In our experience, the rate of growth of tumour is very slow and a wait and watch policy can he adopted for very small tumours and those that are incompletely resected.

Human leptin locus (LEP) alleles and BMI in Samoans.

OBJECTIVES: Because of their location in known candidate gene regions for obesity the associations between six microsatellite markers (D2S2170, D2S144, D2S1268, D2S1788, D2S1348 and a tetranucleotide repeat in the 3' UTR of the LEP locus) and body mass index (BMI) were studied in adult Samoans. DESIGN: The study was designed to detect differences in the proportion of alleles at the six microsatellite markers between two groups of adult Samoans at the extremes of the longitudinal BMI distribution. SUBJECTS AND MEASUREMENTS: The 181 unrelated Samoan participants were 25-55 y of age, reported that all four grandparents were Samoan, resided in American Samoa (AS) or Samoa (S) and were without diagnosed hypertension or type 2 diabetes. Initial statistical analysis was based on chi(2) tests of independence between marker allele frequencies and BMI status at each marker. The association of individual alleles with BMI status was tested by aggregating a marker's allelic data into a two-by-two contingency table and applying a two-tailed version of Fisher's exact test, with a Bonferroni correction to account for the multiple testing implicit in the procedure. RESULTS: There were no significant differences in allele frequencies at any of the markers between AS and S, as expected from our prior population genetic analyses. Only the LEP gene 3'-tetranucelotide repeat was associated (P<0.006) with BMI status. The distribution of the marker alleles at the LEP locus was significantly associated with the BMI groups (P<0.01), due to the low frequency of allele 226 in the high BMI group. The same pattern of association was found in sub-group analyses with low BMI individuals from AS and high BMI individuals from S. CONCLUSION: These findings indicate that the leptin 3'-tetranucleotide repeat is associated with high BMI in adult Samoans, with allele 226 having a low frequency in the high BMI group.

Tuberculosis of the maxillary sinus manifesting as a facial abscess.

Tuberculosis of the maxillary sinus is rare. Likewise, an acute onset that necessitates incision and drainage is also very uncommon. We report the case of a 15-year-old girl who came to us with an abscess on the left side of her face. She was found to have tuberculosis of the left maxillary antrum.

Type 2 diabetes and three calpain-10 gene polymorphisms in Samoans: no evidence of association.

Although genomewide scans have identified several potential chromosomal susceptibility regions in several human populations, finding a causative gene for type 2 diabetes has remained elusive. Others have reported a novel gene, calpain-10 (CAPN10), located in a previously identified region on chromosome 2q37.3, as a putative susceptibility gene for type 2 diabetes. Three single-nucleotide polymorphisms (SNPs) (UCSNP43, UCSNP19, and UCSNP63) were shown to be involved in increased risk of the disease among Mexican Americans. We have tested the association of these three SNPs with type 2 diabetes among the Samoans of Polynesia, who have a very high prevalence of the disease. In the U.S. territory of American Samoa, prevalence is 25% and 15% in men and women, respectively, whereas, in the independent nation of Samoa, prevalence is 3% and 5% in men and women, respectively. In our study sample, which consisted of 172 unrelated affected case subjects and 96 control subjects, we failed to detect any association between case subjects and control subjects in allele frequencies, haplotype frequencies, or haplotype combinations of UCSNP43, -19, and -63. Also, our data showed no evidence of linkage, among 201 affected sib pairs, in the region of chromosome 2 that contains these SNPs. Three plausible scenarios could explain these observations. (1) CAPN10 is a susceptibility gene only in particular ethnic groups; (2) our study lacks power to detect the effects of CAPN10 polymorphisms (but our sample size is comparable to that of earlier reports); or (3) the underlying biological mechanism is too complex and requires further research.

Vertigo syndromes and mechanisms in migraine.

This paper attempts to define and categorize the vertigo associated with migraine. A retrospective chart review of 344 cases of vertigo identified 19 cases with headaches characteristic of migraine as per strictly defined criteria (International Headache Society, 1988). Four distinct types of vertiginous syndromes were noted. The commonest syndrome (Group I) manifested transient episodes of imbalance with additional momentary subjective rotary vertigo worsened by movement. The attacks lasted a few hours and evaluation in the inter-episode interval demonstrated no vestibular deficit. Group II manifested transient objective rotatory vertigo of from 10 minutes to a few hours but no demonstrable permanent vestibular deficit. Group III displayed symptoms and signs characteristic of benign paroxysmal positional vertigo (BPPV) and Group IV manifested a permanent unilateral labyrinthine weakness. Causation of vertigo by migraine was implied in 10 of 19 cases where the headache and vertigo occurred simultaneously and in two other cases where the vertigo improved with anti-migraine prophylactic treatment. Four distinct and characteristic vertigo syndromes have been noted with migraine. Their spectrum ranges from a transient reversible dysfunction to a more permanent destruction, and includes involvement of both the peripheral and the central vestibular systems.

Genomic diversity at thirteen short tandem repeat loci in a substructured caste population, Golla, of southern Andhra Pradesh, India.

Genomic diversity based on 13 short tandem repeat (STR) loci was studied in seven population groups of a substructured Golla caste from Chittoor district in southern Andhra Pradesh, India. These groups are traditionally pastoral, culturally homogeneous, and strictly endogamous. Blood samples were drawn from 317 individuals from 30 Golla villages. The 13 STR loci analyzed in five standard multiplex polymerase chain reactions were: (1) CSF1R, TH01, and PLA2A; (2) F13A1, CYP19, and LPL; (3) D21S1446 and D21S1435; (4) D20S481, D20S473, and D20S604; and (5) D5S1453 and D6S1006. The average heterozygosity was found to be low among the Golla subgroups (0.64-0.70) in comparison to that of groups at the upper levels of the hierarchy. The coefficient of gene differentiation was found to be moderate (average GST = 0.031; range between 0.018 and 0.049 among the loci) when compared to that observed for a similar class of markers among populations with relatively higher levels of hierarchy, for example, among castes. It is, however, much higher when compared to the average observed for Indian caste and tribal populations, based on classical markers. Genetic distance measures revealed clusters of populations that are consistent with the known ethnohistorical and geographical backgrounds of the groups. We claim that these hypervariable markers are quite useful in understanding the process of substructuring within the Indian castes, leading to the formation of smaller breeding isolates, the basic Mendelian units within which microevolutionary forces operate.