Linkage analysis of albuminuria.
American Indians have a higher prevalence of albuminuria than the general population, likely resulting from a combination of environmental and genetic risk factors. To localize gene regions influencing variation in urinary albumin-to-creatinine ratio, we performed a linkage analysis and explored gene-by-diabetes, -hypertension, and -obesity interactions in a large cohort of American Indian families. We recruited >3600 individuals from 13 American Indian tribes from three centers (Arizona, North and South Dakota, and Oklahoma). We performed multipoint variance component linkage analysis in each center as well as in the entire cohort after controlling for center effects. We used two modeling strategies: Model 1 incorporated age, gender, and interaction terms; model 2 also controlled for diabetes, BP, body mass index, HDL, LDL, triglycerides, and smoking status. We evaluated interactions with diabetes, hypertension, and obesity using additive, interaction-specific linkage and stratified analyses. Loci suggestive for linkage to urinary albumin-to-creatinine ratio included 1q, 6p, 9q, 18q, and 20p. Gene-by-diabetes interaction was present with a quantitative trait locus specific to the diabetic stratum in the Dakotas isolated on 18q21.2 to 21.3 using model 1 (logarithm of odds = 3.3). Gene-by-hypertension interaction was present with quantitative trait loci specific to the hypertensive stratum in the Dakotas on 7q21.11 using model 1 (logarithm of odds = 3.4) and 10q25.1 using model 2 (logarithm of odds = 3.3). These loci replicate findings from multiple other genome scans of kidney disease phenotypes with distinct populations and are worthy of further study.
UNC Kidney Center, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7155, USA. amy_mottl@med.unc.edu
Amy K
AK
Mottl
Suma
S
Vupputuri
Shelley A
SA
Cole
Laura
L
Almasy
Harald H H
HH
Göring
Vincent P
VP
Diego
Sandra
S
Laston
Nawar
N
Shara
Elisa T
ET
Lee
Lyle G
LG
Best
Richard R
RR
Fabsitz
Jean W
JW
MacCluer
Jason G
JG
Umans
Kari E
KE
North
D000328:Adult; D000419:Albuminuria / Q000208:ethnology / Q000235:genetics*; D044467:American Indian or Alaska Native / Q000208:ethnology / Q000235:genetics*; D001130:Arizona; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000208:ethnology / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000235:genetics; D007198:Indians, North American / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009658:North Dakota; D009765:Obesity / Q000208:ethnology / Q000235:genetics; D009825:Oklahoma; D040641:Quantitative Trait Loci / Q000235:genetics*; D013023:South Dakota