A genome-wide linkage scan for genes controlling variation in renal function estimated by serum cystatin C levels in extended families with type 2 diabetes
A genome-wide linkage scan for genes controlling variation in renal function estimated by serum cystatin C levels in extended families with type 2 diabetes
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DOI：
10.2337/db06-0781
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发表时间：
2006-12-01
期刊：
影响因子：
7.7
通讯作者：
Krolewski, Andrzej S.
中科院分区：
文献类型：
--
作者：
Placha, Grzegorz;Poznik, G. David;Krolewski, Andrzej S.
我们在63个有多个成员的2型糖尿病大家庭中进行了肾功能的方差成分连锁分析，测量的是肾小球滤过率(GFR)。根据406名糖尿病患者和428名非糖尿病患者亲属的血清半胱氨酸氨基转移酶C和肌酐浓度来评估肾小球滤过率。对半胱氨酸氨基转移酶C的结果进行了总结，因为它们优于肌酐结果。GFR聚集在糖尿病(h(2)=0.45，P<；1×10(-5))和非糖尿病(h 2=0.36，P<；1×10(-3))有显著遗传力(h(2))的家族中。糖尿病亲属与非糖尿病亲属GFR的遗传相关系数r(G)=0.35<1(P=0.01)，提示控制GFR变异的基因不同。连锁结果支持这一解释。在糖尿病亲属中，在染色体2q(优势对数[LOD]4.1)上有很强的连锁，提示在10q(LOD=3.1)和18p(LOD 2.2)上存在连锁。在非糖尿病亲属中，3q(LOD=2.2)和11p(LOD=2.1)上存在连锁。当糖尿病亲属和非糖尿病亲属合并在一起时，仅在7P上发现了连锁的有力证据(LOD=4.0)。总之，在患有和不患有糖尿病的亲属中，部分不同的基因组控制着染色体2q上的GFR变异，前者可能位于10q和18p上，而在两者中可能都位于7p上。这些基因都不与控制尿白蛋白排泄变化的基因重叠。
We performed a variance components linkage analysis of renal function, measured as glomerular filtration rate (GFR), in 63 extended families with multiple members with type 2 diabetes. GFR was estimated from serum concentrations of cystatin C and creatinine in 406 diabetic and 428 nondiabetic relatives. Results for cystatin C were summarized because they are superior to creatinine results. GFR aggregates in families with significant heritability (h(2)) in diabetic (h(2) = 0.45, P < 1 x 10(-5)) and nondiabetic (h 2 = 0.36, P < 1 x 10(-3)) relatives. Genetic correlation (r(G) = 0.35) between the GFR of diabetic and nondiabetic relatives was less than one (P = 0.01), suggesting that genes controlling GFR variation in these groups are different. Linkage results supported this interpretation. In diabetic relatives, linkage was strong on chromosome 2q (logarithm of odds [LOD] 4.1) and suggestive on 10q (LOD = 3.1) and 18p (LOD 2.2). In nondiabetic relatives, linkage was suggestive on 3q (LOD = 2.2) and 11p (LOD = 2.1). When diabetic and nondiabetic relatives were combined, strong evidence for linkage was found only on 7p (LOD = 4.0). In conclusion, partially distinct sets of genes control GFR variation in relatives with and without diabetes on chromosome 2q, possibly on 10q and 18p in the former, and on 7p in both. None of these genes overlaps with genes controlling variation in urinary albumin excretion.