[ 摘要 ]

在台灣原住民高尿酸血症與痛風研究中，發現以布農族、泰雅族及排灣族為主的族群具相當高盛行率，且傾向於家族性聚集之共顯性遺傳。家族性痛風為一複雜性狀疾病，目前尚未發現其候選區域(candidate region)或候選基因(candidate gene)，為找出痛風之主基因(major gene)位置，本研究先以泰雅族部落之痛風家庭來進行疾病基因座之定位。所有樣本來自新竹縣與桃園縣等山地鄉泰雅族部落，共計有23個家庭，154人，家庭成員涵擴一代至三代。以382個多型性遺傳標記STRPs(short tandem repeat polymorphisms)來進行22條體染色體廣泛式基因掃描，並藉由非參數連鎖分析(NPL analysis)與合併傳遞不平衡分析(C-TDT)等遺傳統計分析，來篩選痛風之易感受基因座位置與分析痛風家族世代的遺傳訊息。

發現在體染色體1p32 (D1S2134)、2p25.1 (D2S2952)、4q24-32 (D4S1647)與14q21 (D14S599)等區域，與痛風疾病基因座具有統計意義的連鎖，且這四個區域之至高點位置或附近有遺傳標記與痛風疾病基因座之間具有連鎖與關聯之統計意義，其可輔助加強這些基因座確實可能為痛風的易感受區域，並建議這四個易感受基因座可能為新的痛風候選區域，同時認為痛風應為多基因控制。

[ 英文摘要 ]

In previous studies，we have found there is a high prevalence of hyperuricemia and gout on Taiwanese aborigines, especially on Bunun, Atayal and Paiwan tribes, and the disease trend towards familial aggregation and codominant inheritance. Familiar Gout is a complex trait disorder, and its candidate-region or candidate-gene are not found yet. To find the major gene of gout, this study collected the gout families of Atayal tribe to mapping the gout disease locus. All of samples came from Atayal tribe, included 23 families and their 154 members. We use 382 STRPs (short tandem repeat polymorphisms) markers on 22 autosomal chromosomes for genotyping and naparametric linkage (NPL) analysis and combined transmission/disequilibrium test (C-TDT) for screening susceptibility loci.

By the genome-wide scan, we find regions include 1p32 (D1S2134)、2p25(D2S2952)、4q24(D4S1647, D4S2326) and 14q21(D14S599) have the modest evidence for linkage. Multiple loci in the matched regions display allelic frequently transmission noted at D1S3721 on chromosome 1, D2S2952 on chromosome 2, D4S2623 on chromosome 4, and D14S599 on chromosome 14. Six- and eight-marker haplotypes from the 4q24 region similarly showed transmission in family 9051-1. We suggest the four regions may be worth for further studing candidate genes for familiar gout.