Pérusse L, Rice T, Chagnon Y C, Després J P, Lemieux S, Roy S, Lacaille M, Ho-Kim M A, Chagnon M, Province M A, Rao D C, Bouchard C
Department of Preventive Medicine, Laval University, Ste-Foy, Québec, Canada.
Diabetes. 2001 Mar;50(3):614-21. doi: 10.2337/diabetes.50.3.614.
To identify chromosomal regions harboring genes influencing the propensity to store fat in the abdominal area, a genome-wide scan for abdominal fat was performed in the Quebec Family Study. Cross-sectional areas of the amount of abdominal total fat (ATF) and abdominal visceral fat (AVF) were assessed from a computed tomography scan taken at L4-L5 in 521 adult subjects. Abdominal subcutaneous fat (ASF) was obtained by computing the difference between ATF and AVF. The abdominal fat phenotypes were adjusted for age and sex effects as well as for total amount of body fat (kilogram of fat mass) measured by underwater weighing, and the adjusted phenotypes were used in linkage analyses. A total of 293 microsatellite markers spanning the 22 autosomal chromosomes were typed. The average intermarker distance was 11.9 cM. A maximum of 271 sib-pairs were available for single-point (SIBPAL) and 156 families for multipoint variance components (SEGPATH) linkage analyses. The strongest evidence of linkage was found on chromosome 12q24.3 between marker D12S2078 and ASF (logarithm of odds [LOD] = 2.88). Another marker (D12S1045) located within 2 cM of D12S2078 also provided evidence of sib-pair linkage with ASF (P = 0.019), ATF (P = 0.015), and AVF (P = 0.0007). Other regions with highly suggestive evidence (P < 0.0023 or LOD > or =1.75) of multipoint linkage and evidence (P < 0.05) of single-point linkage, all for ASF, included chromosomes 1p11.2, 4q32.1, 9q22.1, 12q22-q23, and 17q21.1. Three of these loci (1p11.2, 9q22.1, and 17q21.1) are close to genes involved in the regulation of sex steroid levels, whereas two others (4q32.1 and 17q21.1) are in the proximity of genes involved in the regulation of food intake. This first genome-wide scan for abdominal fat assessed by computed tomography indicates that there may be several loci determining the propensity to store fat in the abdominal depot and that some of these loci may influence the development of diabetes in obese subjects.
为了确定含有影响腹部脂肪储存倾向相关基因的染色体区域，在魁北克家族研究中进行了一项全基因组腹部脂肪扫描。对521名成年受试者在L4 - L5水平进行计算机断层扫描，评估腹部总脂肪（ATF）和腹部内脏脂肪（AVF）量的横截面积。腹部皮下脂肪（ASF）通过计算ATF与AVF的差值获得。腹部脂肪表型针对年龄、性别效应以及通过水下称重测量的身体脂肪总量（脂肪质量千克数）进行了调整，并将调整后的表型用于连锁分析。对覆盖22条常染色体的总共293个微卫星标记进行了分型。标记间平均距离为11.9厘摩。最多有271个同胞对可用于单点（SIBPAL）连锁分析，156个家庭可用于多点方差成分（SEGPATH）连锁分析。在12号染色体q24.3上标记D12S2078与ASF之间发现了最强的连锁证据（优势对数[LOD]=2.88）。位于D12S2078的2厘摩范围内的另一个标记（D12S1045）也提供了与ASF（P = 0.019）、ATF（P = 0.015）和AVF（P = 0.0007）的同胞对连锁证据。其他具有多点连锁高度提示性证据（P < 0.0023或LOD >或=1.75）以及单点连锁证据（P < 0.05）的区域，均针对ASF，包括1号染色体p11.2、4号染色体q32.1、9号染色体q22.1、12号染色体q22 - q23和17号染色体q21.1。这些位点中的三个（1号染色体p11.2、9号染色体q22.1和17号染色体q21.1）靠近参与性类固醇水平调节的基因，而另外两个（4号染色体q32.1和17号染色体q21.1）靠近参与食物摄入调节的基因。这项首次通过计算机断层扫描进行的全基因组腹部脂肪扫描表明，可能有几个位点决定腹部脂肪储存倾向，并且其中一些位点可能影响肥胖受试者患糖尿病的风险。
