The cardiovascular risk profile in this population is consistent with metabolic syndrome where low HDL and WHR can be used to predict the risk of CAD. Results suggest the need to redefine the currently practised approach to CAD management in this population to fit local needs.
Refsum's disease (MIM 266500) is a recessive disorder characterised by defective peroxisomal alpha-oxidation of phytanic acid. A Refsum's disease gene, phytanoyl-CoA hydroxylase (PAHX), has been localised to chromosome 10p13 between the markers D10S226-D10S223. This study investigated whether all cases of Refsum's disease were linked with chromosome 10p13. Eight genetically informative families comprising 92 individuals including 17 living patients with a Refsum's disease phenotype and initial plasma phytanic acid > 200 µmol/L were recruited. Linkage to the 10pter-10p11.2 region was investigated using a panel of eight dinucleotide repeat markers. Linkage analysis of this phenotypically identical cohort suggested that Refsum's disease was genetically heterogeneous (Z max = 5.28, α = 0.45). Two subgroups were identified. One group of four families with eight affected individuals had a maximum multipoint lod score for linkage of 3.89 in the region D10S547 to D10S191, whilst in another three families with nine affected individuals linkage to this region was definitely excluded. Our results show that Refsum's disease is genetically heterogeneous, with up to 55% of cases not being linked to the PAHX gene locus at D10S547 to D10S223. This suggests that Refsum's disease, in common with other peroxisomal 'diseases', may be more accurately described as a heterogeneous syndrome.
Abstract-The role of renin-angiotensin system polymorphisms as risk factors for coronary heart disease (CHD) is controversial. This study investigated their role in patients with heterozygous familial hypercholesterolemia (FH). Polymorphism frequencies for angiotensin-I-converting enzyme insertion/deletion (ACE I/D), angiotensinogen M235T, and angiotensin-II type I receptor (AG2R) A1166C were determined in 112 patients with FH and 72 patients with polygenic hypercholesterolemia, of whom 26.7% and 41.6%, respectively, had established CHD. None of the polymorphisms were associated with risk of CHD in patients with polygenic hypercholesterolemia in this study. Key Words: familial hypercholesterolemia Ⅲ coronary artery disease Ⅲ renin-angiotensin system Ⅲ genetics F amilial hypercholesterolemia (FH) is an autosomal dominant disorder of clearance of LDL cholesterol and is associated with premature coronary artery disease. It clinical features include hypercholesterolemia, tendon xanthomata, arcus, and premature atherosclerosis. 1 Patients with heterozygous hypercholesterolemia have significant excess risk at younger ages, although this tends to fall with age to levels 3-to 8-fold greater than those in age-and sex-matched controls. 1,2 The age of onset of coronary heart disease (CHD) in individual families is similar but only moderately correlated with LDL cholesterol concentration and type of mutation. 3 Hence, it is likely that genetic factors beyond the LDL receptor play a role in determining the incidence of CHD in heterozygous FH.The renin-angiotensin system plays a critical role in the control of blood pressure, which is a significant risk factor for atherosclerosis and cardiovascular disease. Recently, polymorphisms in the 3 genes in the renin-angiotensin systemangiotensin-I-converting enzyme deletion/insertion (ACE I/D), the angiotensinogen gene methionine-235 threonine (AGT M235T), and the angiotensin II type I receptor (AG2R) A1166C-have been postulated as risk factors for CHD in patients with polygenic hyperlipidemia. 4 -6 However, the role of these polymorphisms in cardiovascular disease in FH has never been explored. This study examined the role of reninangiotensin polymorphisms in determining the risk of CHD in patients with FH or polygenic hyperlipidemia. Methods SubjectsOne hundred twelve patients with clinical heterozygous FH aged Ͼ40 years and 72 patients with polygenic hyperlipidemia were recruited from the lipid clinics of Guy's and St Thomas' hospitals with local hospital ethical committee permission and after individual informed medical consent had been obtained. The diagnosis of FH was made by Simon Broome Register criteria 1,2 : the presence of an autosomal dominant family history of CHD before age 60 years in first-degree or age 50 years in second-degree relatives, LDL Ͼ5.7 mmol/L (220 mg/dL), and the presence of tendon xanthomata for a definite, as opposed to a probable, diagnosis. The diagnostic criteria for polygenic hyperlipidemia were absence of history of CHD in a first-or second-degree...
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