INS VNTR Class Genotype and Indexes of Body Size and Obesity

Abstract

The relevance of the insulin gene (INS) variable number tandem repeat (VNTR) polymorphism to indexes of body size and adult obesity is inconclusive. Given the equivocal reports on the association between the VNTR class genotype at the insulin gene locus and indexes of body size and obesity, we assessed these associations in a series of cohort studies based on 7,999 middle-aged men and women. We found no convincing evidence that INS VNTR class genotype was associated with indexes of body size and adult obesity. These data suggest that INS VNTR class is not an important determinant of size and body weight regulation in middle-aged men and women. Diabetes 54:2812-2815, 2005 E xperimental and observational studies have suggested that insulin signaling is involved in regulation of somatic growth and body weight (1). The variable number tandem repeat (VNTR) polymorphism, lying 396 base pairs 5Ј to the insulin gene on chromosome 11p15.5, is thought to influence insulin expression (2,3). This minisatellite polymorphism has also been associated with altered expression of the nearby IGF-II, a key regulator of fetal growth and development (4,5). Collectively, observational studies have reported conflicting associations between the INS VNTR class genotype and indexes of body size in childhood and obesity (4,6 -8). Importantly, the relevance of INS VNTR class to indexes of body size and obesity in adults is also inconclusive. Given these equivocal results, we assessed the association between INS VNTR class genotype and indexes of body size and adult obesity in a series of cohort studies based on 7,999 middle-aged men and women. RESEARCH DESIGN AND METHODSWe used data from the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC) and the Ely Study. EPIC is an ongoing prospective cohort study of ϳ25,000 people aged 45-75, resident in Norfolk, and recruited from general practice registers between 1993 and 1997 (9). It is an ethnically homogeneous Caucasian population. These participants completed a health examination. In January 1998, we invited the cohort for a second health examination, and 15,786 people had attended by October 2000. All participants gave informed consent. Details of recruitment, anthropometric measurements, and health examinations following standardized protocols have been published (9). All participants completed a detailed health and lifestyle questionnaire, which included a question on birth weight. A D-loop nonstretch fiberglass tape was used for the head circumference measures. DNA was extracted from the 15,786 whole blood/EDTA samples (Whatman Biosciences, Ely, U.K.) taken at the second health examination. BMI was calculated from the weight and height measures.For the purposes of this analysis, we examined data from two subcohorts of the 15,786 EPIC study participants who attended the second health examination (9). EPIC1 comprises 3,744 participants with fully arrayed DNA available for genotyping. EPIC2 is a random sample of 5,000 participants who were free of baseline disease (ca...

Insulin gene variable number of tandem repeats is not associated with weight from fetal life until infancy: the Generation R Study

“…The genotype distribution (AA 50.8%, AT 40.0%, and TT 9.2%) was similar to those found in previous studies and the frequency distribution did not deviate from the HardyWeinberg equilibrium (c 2 Z1.28, PO0.1) (8,11,19).…”

“…It has also been suggested that this genotype is involved in childhood obesity and the development of metabolic syndrome (13,14), polycystic ovary syndrome (15), and type 2 diabetes in adulthood (16,17). Nevertheless, two large cohort studies were unable to demonstrate effects of INS VNTR on body composition or the risk of metabolic syndrome in adulthood (18,19).…”

Wpływ występowania allelu klasy III VNTR genu INS na parametry auksologiczne, stężenie glukozy, insuliny, lipidów i adipocytokin u przeddojrzewaniowych dzieci urodzonych z niską masą ciała

“…In a general population, other authors also did not support associations between INS VNTR and body composition in childhood [25][26][27][28].…”

“…On the other hand, class III is protective against diabetes mellitus type 1 (T1DM) and leads to an overexpression of insulin [19][20][21]. Thus, it may be responsible for obesity, IR, T2DM, and polycystic ovary syndrome (PCOS); however, the results regarding the influence of INS VNTR polymorphism on these disorders, both in the general population and in SGA individuals, are divergent [10,13,15,17,[22][23][24][25][26][27][28][29]. The aim of the study was to verify whether INS VNTR class III allele is associated with low birth weight in the Polish population and to assess the influence of this variant on the current body mass index (BMI) as well as on the metabolic and hormonal profile in prepubertal SGA children.…”

Association between Polymorphisms of Insulin and Insulin Receptor Gene with Childhood Obesity in Malay Population

“…Polymorphisms of the INS gene have been found to be associated with obesity-related traits in children (Huede et al 2004;Ong et al 2004). However, there are also controversial results showing insignificant association of these polymorphisms with obesity in children or adults (Bouatia-Naji et al 2008;Sandhu et al 2005).…”