Genotype by diabetes interaction effects on the detection of linkage of glomerular filtration rate to a region on chromosome 2q in Mexican Americans.
OBJECTIVE
Glomerular filtration rate (GFR) is used to assess the progression of renal disease. We performed linkage analysis to localize genes that influence GFR using estimated GFR data from the San Antonio Family Diabetes/Gallbladder Study. We also examined the effect of genotype by diabetes interaction (G x DM) on the detection of linkage to address whether genetic effects on GFR differ in diabetic and nondiabetic subjects.


METHODS
GFR (N = 453) was estimated using the recently recalculated Cockcroft-Gault (GFR-CGc) and the simplified Modification of Diet in Renal Disease (GFR-4VMDRD) formulae. Both estimates of GFR exhibited significant heritabilities, but only GFR-CGc showed significant G x DM interaction. We therefore performed multipoint linkage analyses on both GFR measures using models that did not include G x DM interaction effects (Model 1) and that included G x DM interaction effects (Model 2, in the case of GFR-CGc).


RESULTS
The strongest evidence for linkage (Model 1) of both GFR-CGc (logarithm of odds [LOD] 2.9) and GFR-4VMDRD (LOD 2.6) occurred between markers D9S922 and D9S1120 on chromosome 9q. However, using Model 2, the strongest evidence for linkage of GFR-CGc on chromosome 2q was found near marker D2S427 (corrected LOD score [LOD(C)] 3.3) compared with the LOD score of 2.7 based on Model 1. Potential linkages (LOD or LOD(C) >or=1.2) were found only for GFR-CGc on chromosomes 3p, 3q, 4p, 8q, 11q, and 14q.


CONCLUSIONS
We found a major locus on chromosome 2q that differentially influences GFR in diabetic and nondiabetic environments in the Mexican-American population.
Puppala
Sobha
S
Southwest Foundation for Biomedical Research, Department of Genetics, P.O. Box 760549, San Antonio, TX 78254, USA. spuppala@sfbrgenetics.org
Arya
Rector
R
Thameem
Farook
F
Arar
Nedal H
NH
Bhandari
Kusum
K
Lehman
Donna M
DM
Schneider
Jennifer
J
Fowler
Sharon
S
Farook
Vidya S
VS
Diego
Vincent P
VP
Almasy
Laura
L
Blangero
John
J
Stern
Michael P
MP
Duggirala
Ravindranath
R
Abboud
Hanna E
HE
D000328:Adult; D000368:Aged; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003920:Diabetes Mellitus / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics; D005260:Female; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012016:Reference Values