Abstract:
:There is an inverse relationship between serum bilirubin concentrations and risk of coronary artery disease. The strength of the association is similar to that of smoking, systolic blood pressure, and HDL cholesterol. We carried out a genomewide scan in a Framingham Heart Study. Our study sample consisted of 330 families with 1,394 sibling pairs, 681 cousin pairs, and 89 avuncular pairs. Using variance-component methods, the heritability was estimated to be 49%+/-6%, and the genome scan demonstrated significant evidence of linkage of serum bilirubin to chromosome 2q, with a LOD score of 3.8 at location 243 cM. The peak multipoint LOD score is located 1 cM away from the uridine diphosphate glycosyltransferase 1 (UGT1A1) gene. UGT1A1 catalyzes the conjugation of bilirubin with glucuronic acid and thus enhances bilirubin elimination; therefore, it is an important candidate gene for serum bilirubin. Gilbert syndrome, a hyperbilirubinemic syndrome, has a population frequency of 2%-19% and is mainly due to a TA insertion at the promoter region of UGT1A1. Only one other region in the genome produced a multipoint LOD score >1 (LOD = 1.3). Our findings suggest that UGT1A1 may be a major gene controlling serum bilirubin levels in the population.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Lin JP,Cupples LA,Wilson PW,Heard-Costa N,O'Donnell CJdoi
10.1086/373964subject
Has Abstractpub_date
2003-04-01 00:00:00pages
1029-34issue
4eissn
0002-9297issn
1537-6605pii
S0002-9297(07)60625-9journal_volume
72pub_type
杂志文章,多中心研究abstract::Epidermolysis bullosa simplex (EBS) is a dominantly inherited genodermatosis characterized by intraepidermal blister formation. Recent reports have suggested that EBS mutations may relate to keratin abnormalities. In this study, we conducted RFLP analyses to test the hypothesis that EBS is linked to one of the keratin...
journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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journal_title:American journal of human genetics
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章,多中心研究
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journal_title:American journal of human genetics
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