Haplotype diversity in four genes (CLCNKA, CLCNKB, BSND, NEDD4L) involved in renal salt reabsorption.

نویسندگان

  • Saba Sile
  • Digna R Velez
  • Niloufar B Gillani
  • Charles A Alexander
  • Alfred L George
  • Scott M Williams
چکیده

OBJECTIVE Differences exist among various populations with regards to hypertension prevalence, severity, progression and response to therapy. Such differences may be due to genetic or environmental factors. We characterized the genetic variation and haplotype diversity of four hypertension candidate genes (CLCNKA, CLCNKB, BSND, NEDD4L) in four different ethnic groups (Caucasian Americans, African-Americans, Han Chinese, and Mexican-Americans). METHODS We genotyped 42 single nucleotide polymorphisms across the four genes in equal numbers of each ethnically defined population, then tested for linkage disequilibrium, computed allelic and haplotype frequencies, and compared data across the different ethnic groups. RESULTS We identified significant genotype and allele frequency differences among ethnic groups. The strongest differences were observed between African-American and Mexican-Americans and between Caucasian and Mexican-Americans. In addition, haplotype blocks were defined for BSND, CLCNKA_B and NEDD4L in the four populations examined. Completely mismatched ('yin yang') haplotypes were also observed. We found that the number of inferred halpotypes varied gene to gene and in some instances between the populations for a given gene indicating substantial haplotype diversity. The haplotype diversity among the various ethnic populations observed in our study was greater than that reported in Perlegen database. CONCLUSIONS Haplotype diversity in hypertension candidate genes has important implications for designing and evaluating candidate gene or genome-wide blood pressure association studies that consider these genes.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Common genetic variants and haplotypes in renal CLCNKA gene are associated to salt-sensitive hypertension.

Abnormal renal reabsorption of sodium (Na(+)) is likely to play a role in the pathogenesis of salt-sensitivity. In the kidney, chloride channels CLC-Ka (gene CLCNKA) and CLC-Kb (gene CLCNKB) and their subunit Barttin (gene BSND) have important effects on the control of Na(+) and water homeostasis. We investigated if single nucleotide polymorphisms (SNPs) or haplotypes within CLCNKA, CLCNKB and ...

متن کامل

Functional significance of channels and transporters expressed in the inner ear and kidney.

A number of ion channels and transporters are expressed in both the inner ear and kidney. In the inner ear, K(+) cycling and endolymphatic K(+), Na(+), Ca(2+), and pH homeostasis are critical for normal organ function. Ion channels and transporters involved in K(+) cycling include K(+) channels, Na(+)-2Cl(-)-K(+) cotransporter, Na(+)/K(+)-ATPase, Cl(-) channels, connexins, and K(+)/Cl(-) cotran...

متن کامل

Inherited renal tubulopathies associated with metabolic alkalosis: effects on blood pressure.

Inherited tubular disorders associated with metabolic alkalosis are caused by several gene mutations encoding different tubular transporters responsible for NaCl renal handling. Body volume and renin-angiotensin-aldosterone system status are determined by NaCl reabsorption in the distal nephron. Two common hallmarks in affected individuals: hypokalemia and normal / high blood pressure, support ...

متن کامل

Molecular biology of hereditary diabetes insipidus.

The identification, characterization, and mutational analysis of three different genes-the arginine vasopressin gene (AVP), the arginine vasopressin receptor 2 gene (AVPR2), and the vasopressin-sensitive water channel gene (aquaporin 2 [AQP2])-provide the basis for understanding of three different hereditary forms of "pure" diabetes insipidus: Neurohypophyseal diabetes insipidus, X-linked nephr...

متن کامل

Clinical and diagnostic features of Bartter and Gitelman syndromes

Background: Bartter and Gitelman syndromes are autosomal recessive disorders of renal tubular salt handling. Due to their rarity, limited long-term data are available to inform prognosis and management. Methods: Long-term longitudinal data were analysed for 45 children with pathogenic variants in SLC12A1 (n 1⁄4 8), KCNJ1 (n 1⁄4 8), CLCNKB (n 1⁄4 17), BSND (n 1⁄4 2) and SLC12A3 (n 1⁄4 10) seen a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Human heredity

دوره 65 1  شماره 

صفحات  -

تاریخ انتشار 2008