Lipoprotein (a) as an independent risk factor for myocardial infarction in patients with common hypercholesterolaemia.

AIMS: To examine whether lipoprotein (a) (Lp(a)) increases the risk of myocardial infarction (MI) in patients with common hypercholesterolaemia. METHODS: 15 middle aged men with common hypercholesterolaemia (mean serum low density lipoprotein (LDL) cholesterol 4.94 mmol/l, SD 1.0) and a history of MI were selected consecutively from referrals to a lipid clinic. A control group that had not sustained an MI and with similar age, sex, cigarette smoking and blood pressure characteristics was also selected from the same clinic. Serum cholesterol, triglyceride, LDL cholesterol, high density lipoprotein cholesterol, apolipoproteins AI and B and Lp(a) were measured in both groups. Lp(a) was assayed by immunoturbidity. RESULTS: The serum concentration of Lp(a) was significantly higher in patients with MI (geometric mean 0.64 (95% confidence interval 0.36 to 1.14) v 0.30 (0.21 to 0.42) g/l, p = 0.02), but there were no significant differences in other variables. Stepwise logistic regression analysis showed that Lp(a) was the only significant predictor of MI (p < 0.02). The odds ratio of MI (adjusted for age, smoking, blood pressure and apolipoprotein B) for an Lp(a) of > 0.57 g/l was 16.5, 95% confidence interval 2.3 to 125.4 (p = 0.001). CONCLUSION: In middle aged men with common hypercholesterolaemia the serum concentration of Lp(a) is a powerful and independent risk factor for MI. Lp(a) should probably be routinely measured in all patients referred to a lipid clinic.     

AMP-18,一种新发现的胃黏膜保护因子

AMP-18是一种新发现的由胃腺体上皮细胞合成的小分子蛋白质,独特表达于胃黏膜,机体其他部位少见,胃癌组织中表达缺失．AMP-18 由185个氨基酸组成,除去N端信号肽(20个氨基酸)后大小约18 ku,第54-150个氨基酸组成高度保守的结构域(BRICHOS区域)承担主要的生理功能．AMP-18由胃腺体上皮细胞以胞吐的方式分泌到胃黏液中,他的合成和分泌与个体生长发育有关,并受福斯高林、吲哚美辛、地塞米松等药物的影响．目前发现 AMP-18的生理功能主要有促进胃黏膜上皮细胞的有丝分裂,促进细胞的迁徙,促胃肠黏膜损伤的修复,保持胃肠黏膜的完整等．     

Genetic screening for autosomal recessive nonsyndromic mental retardation in an isolated population in Israel

Nonsyndromic mental retardation (NSMR) is the diagnosis of exclusion in mentally retarded individuals without additional abnormalities. We have recently identified a protein-truncating mutation, G408fsX437, in the gene CC2D1A on chromosome 19p13.12 in nine consanguineous Israeli Arab families with severe autosomal recessive NSMR, and have developed a comprehensive prevention program among the at-risk population in the village. The subjects tested were healthy women who were invited to undergo the genetic screening test as a part of their routine pregnancy monitoring. One hundred and seventeen subjects reported a family history positive for mental retardation. We tested 524 pregnant or preconceptional women and found 47 carriers (approximately 1/11), whose spouses were then recommended to undergo testing. We identified eight carrier couples, who were given genetic counseling and offered prenatal diagnosis. Of all the marriages, 28.6% were consanguineous; 16.5% of the total were between first cousins. The high prevalence of the mutation can be explained both by the founder effect owing to the generally high consanguinity rate among the inhabitants of the village, and also because two families with excessive numbers of mentally retarded offspring were unacceptable as marriage partners by the rest of the families. This is the first example of the establishment of a large-scale genetic screening program for autosomal recessive NSMR, which was made possible owing to the high frequency of the specific causative mutation in this isolated population.     

A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders

Innes AM, Boycott KM, Puffenberger EG, Redl D, MacDonald IM, Chudley AE, Beaulieu C, Perrier R, Gillan T, Wade A, Parboosingh JS. A founder mutation in BBS2 is responsible for Bardet‐Biedl syndrome in the Hutterite population: utility of SNP arrays in genetically heterogeneous disorders. Bardet‐Biedl syndrome (BBS) is a multisystem genetically heterogeneous disorder, the clinical features of which are largely the consequence of ciliary dysfunction. BBS is typically inherited in an autosomal recessive fashion, and mutations in at least 14 genes have been identified. Here, we report the identification of a founder mutation in the BBS2 gene as the cause for the increased incidence of this developmental disorder in the Hutterite population. To ascertain the Hutterite BBS locus, we performed a genome‐wide single nucleotide polymorphism (SNP) analysis on a single patient and his three unaffected siblings from a Hutterite family. The analysis identified two large SNP blocks that were homozygous in the patient but not in his unaffected siblings, one of these regions contained the BBS2 gene. Sequence analysis and subsequent RNA studies identified and confirmed a novel splice site mutation, c.472‐2A>G, in BBS2. This mutation was also found in homozygous form in three subsequently studied Hutterite BBS patients from two different leuts, confirming that this is a founder mutation in the Hutterite population. Further studies are required to determine the frequency of this mutation and its role, if any, in the expression of other ciliopathies in this population.