Familial components of the multiple metabolic syndrome: the ARIC Study

Abstract

The clustering of multiple metabolic abnormalities including obesity, insulin resistance, non-insulin-dependent diabetes mellitus (NIDDM), hypertension, and dyslipidaemias has become known as the insulin resistance syndrome [1,2] or multiple metabolic syndrome (MMS) [3,4]. Genetic as well as shared environmental influences on insulin, insulin resistance, and obesity have been reported in family and twin studies [5][6][7][8][9][10][11]. Familial aggregation of NIDDM [12,13], elevated blood pressure levels [14,15], and lipid disorders [16,17] is well established. Metabolic disorders such as familial hypercholesterolaemia [18,19], familial combined hyperlipidaemia [20][21][22], and familial dyslipidemic hypertension [23] require a positive family history as part of their definition.Particularly within genetic epidemiology, studies on the MMS have frequently had a primary focus on a single, continuously distributed metabolic characteristic such as insulin [8,9]. Others have compared multiple metabolic variables among offspring of affected and unaffected parents [24][25][26][27][28][29][30][31]. Focusing on a single metabolic characteristic, however, limits the Diabetologia (1997) Summary The association of a parental history of diabetes mellitus and hypertension with the multiple metabolic syndrome (MMS) was studied in a population survey of middle-aged adults. The eligible population was drawn from the baseline examination of the Atherosclerosis Risk in Communities Study, a population-based, bi-ethnic, multi-centre cohort study. The MMS was defined as a multivariate, categorical phenotype of co-occurring diabetes, hypertension, and dyslipidaemia. MMS cases (n = 356) were compared to disorder-free control subjects (n = 6797) with respect to their parental history of diabetes and hypertension. MMS cases were more likely to report a history of diabetes in both parents (odds ratio [OR] 4.7, 95 % confidence interval (CI) 1.5-14.7) or a history of hypertension in both parents (OR 1.9, 95 % CI 1.1-3.0) than control subjects, adjusting for BMI, waist-to-hip ratio, age, gender, and ethnicity/centre. A parental history of diabetes and hypertension in both parents was associated with the greatest increase in odds of MMS (OR 8.3,. A dose-response relationship between the number of parental disorders (one; two; three to four) and the odds of MMS was observed (OR 1.2, 95 % CI 0.9-1.7; OR 2.0, 95 % CI 1.4-2.8; OR 4.0, 95 % CI 2.5-6.2). Based on the marked associations observed between a parental history of MMS components and the clustering of these metabolic disorders in the offspring generation, we conclude that genetic and/or non-genetic familial influences play a role in the development of the multiple metabolic syndrome. [Diabetologia (1997) 40: 963-970]

Influence of parental history of hypertension on blood pressure

“…The same relationship was found by other authors after adjustment for age, 21 for age and sex, 13 for sex, age and skinfold, 14 and after adjustment for BMI, waistto-hip ratio, sex, age and ethnicity/centre. 22 In our work, after adjustment for several clinical and environmental factors related to hypertension such as age, BMI, sedentary lifestyle, tobacco and alcohol consumption, diabetes, hypercholesterolaemia, the significant relationship remained both in women and men. Like other studies, 16,23,24 the values of systolic and diastolic blood pressure (у160 and 95 mm Hg) were used for the analysis according to the previous WHO recommendations.…”

Association between C-reactive protein and features of the metabolic syndrome: a population-based study.

“…Although both hereditary (6,7) and environmental factors contribute to the development of the MS, little is known about the underlying pathogenetic mechanisms. However, a central role has been attributed to the proinflammatory cytokines tumor necrosis factor-␣ (TNF-␣) (8) and interleukin (IL)-6 (9), supported by the fact that both are produced in substantial amounts by human adipose tissue.…”

Genome-wide Scan for Metabolic Syndrome and Related Quantitative Traits in Hong Kong Chinese and Confirmation of a Susceptibility Locus on Chromosome 1q21-q25

“…A common latent genetic factor may influence the clustering of traits (10,11). Type 2 diabetes and hypertension show familial aggregation of MES (12). Bivariate genetic analyses in families suggest a pleiotropic effect between insulin level and obesity indexes or lipids (13,14) and between obesity indexes and lipids (15).…”