Tetranucleotide Repeat Polymorphism Research Articles

Development of the X-linked tetrameric microsatellite marker HumDXS6789 for forensic purposes

This paper presents sequence and population genetic data of the X-linked DXS6789 short tandem repeat (STR). The tetranucleotide repeat polymorphism DXS6789, also known as CHLC.GATA31F01, is located at the Xq22.3 region. This locus is unlinked with DXS6807 and slightly linked with ARA, DXS9898 and HPRTB. In kinship testing, DXS6789 is suitable for concomitant use with DXS6807. Population genetic data were obtained by analysing 250 unrelated males and 315 females from East Germany. In this population, the STR exhibited 12 clearly distinguishable alleles ranging from 154 to 198 bps in length. DXS6789 is characterised by the following data: polymorphic information content (PIC)=0.70; observed heterozygosity (Het)=0.78; mean exclusion chance (MEC)=0.70. A deviation from the Hardy–Weinberg equilibrium could not be detected. The investigations we performed in 243 mother–child and 161 father–child meioses did not reveal any mutations.

Polymorphism of the aromatase gene in postmenopausal Italian women: distribution and correlation with bone mass and fracture risk.

Conversion of C(19) steroids to estrogens is catalyzed by the aromatase enzyme. Inactivating mutations of the aromatase gene are associated with decreased bone mineral density in both men and women. Genetic studies suggest that several genes contribute to the regulation of bone mass via interaction with the modeling and remodeling processes. Among these genes, the aromatase gene is a potential candidate to be evaluated for segregation with bone metabolism and bone mass. A tetranucleotide simple tandem repeat polymorphism in intron 4 at the human aromatase cytochrome P-450 gene has been recently described. In the present study we evaluated the distribution of this polymorphism in a cohort of Italian postmenopausal women, both normal and osteoporotic. We observed that the NN genotype was significantly more frequent in nonosteoporotic women than in osteoporotic women (72.7% vs. 27.2%), whereas the DN genotype was significantly more represented in osteoporotic women (90.48% vs. 9.5%; Pearson's chi(2) test = 42.8; df = 10; P = or < 0.01). The allele containing the longer TTTA repeats was statistically more represented in nonosteoporotic women (Pearson's chi(2) test = 19.14; df = 2; P = 0.00007). In addition, women with a high number of TTTA repeats had a significantly higher lumbar bone mineral density than women with alleles containing 8-11 TTTA repeats (P = 0.03). Finally, considering the spine fractures, a significantly higher incidence was observed in women with shorter TTTA repeats than in those with longer TTTA repeats (Pearson's chi(2) test = 7.3; df = 2; P = 0.02), equivalent to a relative risk of 4.1 (95% confidence interval, 1.19-13.87). In conclusion, the aromatase gene can be one of the several genes potentially involved in the maintenance of bone mass and in the regulation of bone mass loss.

Prostate carcinoma risk and allelic variants of genes involved in androgen biosynthesis and metabolism pathways.

Ethnicity, when it is used to mean shared genetic inheritance within a group, has become one of the most important factors in determining prostate carcinoma risk. Genetic polymorphisms were hypothesized to be the probable explanation for differences in risk among ethnic groups. The authors evaluated the association between polymorphisms in genes involved in the androgen biosynthesis and metabolism pathway and the risk of prostate carcinoma. Two hundred twenty-six patients with the pathologic diagnosis of sporadic prostate tumor and 156 healthy matched (age, ethnic group) male controls from a large epidemiologic cohort were genotyped for previously described polymorphisms in the androgen receptor (AR), 5alpha-reductase type II (SRD5A2), p450c17 (CYP17), and aromatase (CYP19) genes. The different polymorphisms in prostate carcinoma patients also were analyzed according to age of onset, preoperative prostate-specific antigen level, tumor stage, and tumor grade. The distribution of the tetranucleotide simple tandem repeat polymorphism (STRP) in intron 4 of CYP19 was significantly different in control and cancer patients (P = 0.012). The 171 allele and the 187 allele were associated with prostate carcinoma risk (P = 0.05 and P = 0.045, respectively). Conversely, no association was observed between prostate carcinoma risk and the other polymorphisms studied as follow: the CAG repeat in exon 1 of AR, the (TA)n dinucleotide repeat polymorphism in the 3' untranslated region, and the A49T or V89L substitutions in SDR5A2, the single base pair (bp) (a T to C transition) polymorphism that creates an additional Sp1-type (CCACC box) promoter site in CYP17. In prostate carcinoma patients, CAG repeats of AR, and TA repeats of SDR5A2 are associated with age of onset (P = 0.05 and P < 0.001, respectively). The association between the 171-bp allele of CYP19 and prostate carcinoma risk suggests that aromatase could be used as a new indicator for prostate carcinoma prevention in men of White French ethnogeographic origin. Conversely, it is possible that an individual carries both a high- and a low-risk marker (e.g., CYP17 A2 allele and V89L in SRD5A2) resulting in no overall difference in risk observed across the population. For these reasons, the development of a polygenic model, incorporating multiple loci from the individual genes may maximize the chance of identifying individuals with high-risk genotypes.

Association between triglyceride-rich lipoprotein remnant receptor polymorphisms and lipid traits

Objectives: The metabolism of triglyceride-rich lipoproteins (TRL) is, in part, mediated by lipoprotein receptors (such as low density lipoprotein receptor-related protein [LRP] and very low density lipoprotein [VLDL] receptors), which recognize TRL remnants after specific binding with apolipoprotein E. The purpose of this study was to explore the association of the genetic polymorphisms of remnant receptors with lipid, lipoprotein, and apolipoprotein levels including remnant-like particle-cholesterol (RLP-C). Design and Methods: Using polymerase chain reaction-amplified DNA, VLDL receptor tetranucleotide repeat polymorphism, LRP trinucleotide repeat polymorphism, and LRP exon 3 polymorphism were analyzed in normal adults (control group: n = 161) and in patients with coronary artery disease (CAD group: n = 102). Results: The allelic distributions of VLDL receptor triple repeat polymorphism, LRP tetranucleotide repeat polymorphism, and LRP exon 3 polymorphism in Koreans were similar to those of Japanese but were significantly different from those of other ethnic groups. There were no significant differences in the allele frequencies of the polymorphisms between the control and CAD groups. VLDL receptor polymorphism in the control group (p = 0.0403) and LRP exon 3 polymorphism in the CAD group ( p = 0.0459) showed significant associations with lipoprotein (a) [Lp(a)] levels. Conclusions: The results of the present study demonstrated significant interracial distribution of remnant receptor polymorphisms. There was no association between the remnant receptor polymorphisms and the RLP-C levels. However, the polymorphisms showed a significant association with Lp(a), which may suggest that the Lp(a) metabolism is in part mediated by the uptake through the remnant receptors.

Confirmation of the Assignment of the Dombrock Blood Group Locus (DO) to Chromosome 12p: Narrowing the Boundaries to 12p 12.3‐p13.2

Abstract Background and Objectives : Antigens belonging to the Dombrock blood group system have been well characterized serologically. Despite being reasonably polymorphic, chromosomal localization of the gene controlling Dombrock expression (DO) has proved difficult. In the past, DO had been provisionally assigned to chromosomes 1 and 4; more recently, DO was provisionally assigned to chromosome 12. The current study was undertaken in an attempt to confirm or refute this latest assignment. Materials and Methods: DNA from a series of families segregating for DO was amplified by polymerase chain reaction and analyzed for trinucleotide or tetranucleotide repeat polymorphisms of four anonymous DNA markers (D12S1042, D12S373, D12S391, D12S372) and of the von Willebrand factor gene (VWF). Lods for or against linkage were determined between DO and each marker. Results: DO is linked to all five markers. The closest linkage was established between DO and D12S373, and DO and D12S391, with peak lods for combined paternal and maternal meioses of 7.16 at peak recombination fraction ( ) = 0.08 and 7.69 at = 0.08, respectively. Conclusions: We have confirmed the assignment of the Dombrock blood group locus to chromosome 12p and have refined its regional localization to 12p 12.3–p 13.2.

Confirmation of the Assignment of the Dombrock Blood Group Locus (DO) to Chromosome 12p: Narrowing the Boundaries to 12p12.3–p13.2

Background and Objectives: Antigens belonging to the Dombrock blood group system have been well characterized serologically. Despite being reasonably polymorphic, chromosomal localization of the gene controlling Dombrock expression (DO) has proved difficult. In the past, DO had been provisionally assigned to chromosomes 1 and 4; more recently, DO was provisionally assigned to chromosome 12. The current study was undertaken in an attempt to confirm or refute this latest assignment. Materials and Methods: DNA from a series of families segregating for DO was amplified by polymerase chain reaction and analyzed for trinucleotide or tetranucleotide repeat polymorphisms of four anonymous DNA markers (D12S1042, D12S373, D12S391, D12S372) and of the von Willebrand factor gene (VWF). Lods for or against linkage were determined between DO and each marker. Results: DO is linked to all five markers. The closest linkage was established between DO and D12S373, and DO and D12S391, with peak lods for combined paternal and maternal meioses of 7.16 at peak recombination fraction (θcirc;) = 0.08 and 7.69 at θcirc; = 0.08, respectively. Conclusions: We have confirmed the assignment of the Dombrock blood group locus to chromosome 12p and have refined its regional localization to 12p12.3–p13.2.

Search for the influence of the tyrosine hydroxylase (TCAT) n repeat polymorphism on personality traits

A putatively functional tetranucleotide repeat polymorphism in the tyrosine hydroxylase gene (TH) has been investigated with regard to different aspects of psychopathology. We investigated whether reported associations of this TH polymorphism may reflect associations with common personality traits. Personality was assessed by the NEO Personality Inventory-Revised version (NEO PI-R), in 205 healthy Caucasian volunteers. Tendencies for higher scores in the neuroticism (N) facets, Angry hostility ( P=0.008) and Vulnerability ( P=0.021), were observed among carriers of one of the alleles (T8). Healthy women with the T6/T10 genotype had significantly higher scores ( P=0.001) in the Deliberation and Dutifulness facets ( P=0.031) (the Conscientiousness dimension, C) and lower scores ( P=0.031) in the Feelings facet (the Openness dimension, O). We concluded that: (1) higher mean scores in the Neuroticism facets among T8 allele carriers are consistent with previous data and warrants further research; (2) the T6/T10 genotype may influence personality among women; (3) these data should be cautiously interpreted in the absence of corroborating data.

A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk

The CYP19 gene codes for aromatase, a key steroidogenic enzyme involved in the conversion of androgens to estrogens. A tetranucleotide (TTTA) repeat polymorphism is present in intron 4 of CYP19; 2 out of 4 breast cancer case-control studies have reported a greater frequency of 2 specific alleles among affected women. We evaluated associations between CYP19 repeat alleles and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort (incident cases: n=462; controls: n=618). We observed seven different CYP19 alleles (TTTA(7-13)). Compared to controls, cases had a statistically significant greater frequency of the 10 (TTTA)(10) repeat allele (10 allele: 2.3% vs. 0.7%, p = 0.005) and a nonsignificant increase in the frequency of the 12 (TTTA)(12) allele (12 allele: 3.1% vs. 2.1%, p = 0.11). A higher frequency of the 10 allele was observed in more advanced cancer cases defined as four or more involved nodes or distant metastasis [4+ nodes: 5/36 (13.9%) vs. 0-3 nodes: 13/330 (3.9%), p = 0.02]. Among controls, we found women with the 7 repeat allele to have decreased levels of estrone sulfate (-16.4%, p = 0.02), estrone (-6.1%, p = 0.22) and estradiol (-9.9%, p = 0.10), and a lower estrone/androstenedione ratio (E1/A) (-10.5%, p = 0.08) compared to non-carriers. A higher E1/A ratio and elevated estrogen levels were observed among carriers of the 8 repeat allele; E1/A ratio (+21.0%, p = 0.003), estrone (+7.5%, p = 0.16) and estradiol (+10.8%, p = 0.08). However, we observed no evidence of an association between these alleles and breast cancer risk. We were unable to make inferences regarding the effect of the 10 allele on hormone levels due to the small number of allele carriers in the subgroup with hormone levels. As this repeat polymorphism is not close to the splice sites in intron 4, linkage disequilibrium with other functional polymorphisms in CYP19 may explain the findings of an increased association between breast cancer and the 10 allele variant of CYP19. We did not detect any sequence variants in the regulatory region or in the adipose-specific exon I.4. The lack of an established effect on CYP19 function associated with the 10 allele means that these findings should be interpreted with caution.

Association study of a new polymorphism in the PECAM-1 gene in multiple sclerosis

Genetic polymorphisms of immunorelevant genes may modulate occurrence or clinical features of multifactorial diseases. PECAM-1 is an adhesion molecule crucial for transmigration of cells from blood to tissues, but its genetic contribution to multifactorial diseases has never been investigated. We have identified and characterized a tetranucleotide repeat polymorphism within the third intron of PECAM-1. In a cohort of healthy controls (HC), we found 10 alleles. An assessment of the association of this polymorphism with multiple sclerosis (MS) showed similar allele and genotype frequencies in HC and MS patients as well as in MS patients differing for the gravity of their disease course. We conclude that although potentially able to affect organ-specific autoimmune diseases, this new PECAM-1 polymorphism, does not seem to contribute to the genetic background of MS.

A polymorphic tetranucleotide repeat in the CYP19 gene and male breast cancer.

The CYP19 gene codes for the aromatase enzyme that is involved in the synthesis of oestrogens. This case–control study examines the relationship between a tetranucleotide repeat sequence in the CYP19 gene and the development of male breast cancer. No significant differences were found between male breast cancer cases and controls. © 2000 Cancer Research Campaign

A tetranucleotide repeat polymorphism inCYP19 and breast cancer risk

The CYP19 gene codes for aromatase, a key steroidogenic enzyme involved in the conversion of androgens to estrogens. A tetranucleotide (TTTA) repeat polymorphism is present in intron 4 of CYP19; 2 out of 4 breast cancer case-control studies have reported a greater frequency of 2 specific alleles among affected women. We evaluated associations between CYP19 repeat alleles and breast cancer risk in a case-control study nested within the Nurses' Health Study cohort (incident cases: n=462; controls: n=618). We observed seven different CYP19 alleles (TTTA7–13). Compared to controls, cases had a statistically significant greater frequency of the 10 (TTTA)10 repeat allele (10 allele: 2.3% vs. 0.7%, p = 0.005) and a nonsignificant increase in the frequency of the 12 (TTTA)12 allele (12 allele: 3.1% vs. 2.1%, p = 0.11). A higher frequency of the 10 allele was observed in more advanced cancer cases defined as four or more involved nodes or distant metastasis [4+ nodes: 5/36 (13.9%) vs. 0–3 nodes: 13/330 (3.9%), p = 0.02]. Among controls, we found women with the 7 repeat allele to have decreased levels of estrone sulfate (−16.4%, p = 0.02), estrone (−6.1%, p = 0.22) and estradiol (−9.9%, p = 0.10), and a lower estrone/androstenedione ratio (E1/A) (−10.5%, p = 0.08) compared to non-carriers. A higher E1/A ratio and elevated estrogen levels were observed among carriers of the 8 repeat allele; E1/A ratio (+21.0%, p = 0.003), estrone (+7.5%, p = 0.16) and estradiol (+10.8%, p = 0.08). However, we observed no evidence of an association between these alleles and breast cancer risk. We were unable to make inferences regarding the effect of the 10 allele on hormone levels due to the small number of allele carriers in the subgroup with hormone levels. As this repeat polymorphism is not close to the splice sites in intron 4, linkage disequilibrium with other functional polymorphisms in CYP19 may explain the findings of an increased association between breast cancer and the 10 allele variant of CYP19. We did not detect any sequence variants in the regulatory region or in the adipose-specific exon I.4. The lack of an established effect on CYP19 function associated with the 10 allele means that these findings should be interpreted with caution. Int. J. Cancer 87:204–210, 2000. © 2000 Wiley-Liss, Inc.

Validation of the HumDXS6807 short tandem repeat polymorphism for forensic application.

This paper presents sequence and population genetic data of the HumDXS6807 short tandem repeat (also known as CHLC.GATA52B03) which is a tetranucleotide repeat polymorphism representing seven alleles of 251-275 bp in length. HumDXS6807 is located at Xpter-Xp22.2, i.e., at a genetic distance of more than 87 and 151 cM from the well-known markers HumARA and HumHPRTB, respectively. Kinship tests in 157 family trios revealed a typical X-linked codominant inheritance; mutations were not found. Population genetic data were obtained by analyzing a Caucasian population sample comprising 308 females and 209 males: polymorphism information content (PIC) = 0.640; Heterozygosity (Het) = 0.668; Mean exclusion chance (MEC) = 0.414. The HumDXS6807 allele distribution met the Hardy-Weinberg expectations.

Isolation, genomic organization, and expression analysis of Men1, the murine homolog of the MEN1 gene.

The mouse homolog of the human MEN1 gene, which is defective in a dominant familial cancer syndrome, multiple endocrine neoplasia type 1 (MEN1), has been identified and characterized. The mouse Men1 transcript contains an open reading frame encoding a protein of 611 amino acids which has 97% identity and 98% similarity to human menin. Sequence of the entire Men1 gene (9.3 kb) was assembled, revealing 10 exons, with exon 1 being non-coding; a polymorphic tetranucleotide repeat was located in the 5'- flanking region. The exon-intron organization and the size of the coding exons 2-9 were well conserved between the human and mouse genes. Fluorescence in situ hybridization localized the Men1 gene to mouse Chromosome (Chr) 19, a region known to be syntenic to human Chr 11q13, the locus for the MEN1 gene. Northern analysis indicated two messages-2.7 kb and 3.1 kb-expressed in all stages of the embryo analyzed and in all eight adult tissues tested. The larger transcript differs from the smaller by the inclusion of an unspliced intron 1. Whole-mount in situ hybridization of 10.5-day and 11.5-day embryos showed ubiquitous expression of Men1 RNA. Western analysis with antibodies raised against a conserved C-terminal peptide identified an approximately 67-kDa protein in the lysates of adult mouse brain, kidney, liver, pancreas, and spleen tissues, consistent with the size of human menin. The levels of mouse menin do not appear to fluctuate during the cell cycle.

Analysis and metaanalysis of two polymorphisms within the tyrosine hydroxylase gene in bipolar and unipolar affective disorders.

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in the synthesis of dopamine and noradrenaline. While positive associations between TH and bipolar affective disorder have been found in several studies, many studies have failed to reproduce these results. In order to clarify this situation, association studies of bipolar and unipolar affective disorder groups and metaanalyses of published data on the TH tetranucleotide repeat polymorphism were done. The association studies used the TH tetranucleotide repeat polymorphism in intron 1 and a PstI polymorphism at the 3' end of the gene. The study comprised 124 unrelated bipolar patients, 126 unipolar patients, and 242 controls. There was no significant association of either bipolar or unipolar affective disorder with the TH tetranucleotide repeat polymorphism. However, a weak association (chi2 = 3.946, 1 df, P = 0.047; odds ratio, allele 2 vs. allele 1 = 0.71 (95% CI, 0.51-0.996)) was observed in the unipolar sample with the TH-PstI polymorphism. Three metaanalyses of published data on the TH tetranucleotide repeat polymorphism in major affective disorder were performed: bipolar I + II vs. control using 583 cases and 745 controls; unipolar vs. control using 204 cases and 359 controls; and bipolar + unipolar vs. control using 846 cases and 823 controls. In each analysis there was no association of the TH tetranucleotide repeat polymorphism and affective disorder. These results do not support the tyrosine hydroxylase gene having a major role in the etiology of bipolar affective disorder. However, our data suggest that this locus should be examined in larger samples of unipolar affective disorder.

Constitutional genetic variation at the human aromatase gene (Cyp19) and breast cancer risk.

The activity of the aromatase enzyme, which converts androgens into oestrogens and has a major role in regulating oestrogen levels in the breast, is thought to be a contributing factor in the development of breast cancer. We undertook this study to assess the role of constitutional genetic variation in the human aromatase gene (Cyp19) in the development of this disease. Our genotyping of 348 cases with breast cancer and 145 controls (all Caucasian women) for a published tetranucleotide repeat polymorphism at intron 4 of the Cyp19 gene revealed the presence of six common and two rare alleles. Contingency table analysis revealed a significant difference in allelic distribution between cases and controls (χ2 5df = 13.52, P = 0.019). The allele measuring 171 bp was over-represented in cases; of 14 individuals homozygous for this allele, 13 were cases. These individuals had a higher incidence of cancer in family members and an earlier age at diagnosis than other cases. In sequencing Cyp19's coding exons and regulatory regions, we discovered a perfect association between a silent polymorphism (G→A at Val80) and the high-risk genotype. Our conclusion is that constitutional genetic variation at the Cyp19 locus is associated with the risk of developing breast cancer, with the 171-bp allele serving as the high-risk allele. © 1999 Cancer Research Campaign

Polymorphism at the tetranucleotide repeat locus DYS389 in 10 populations reveals strong geographic clustering.

Several short tandem repeat polymorphism loci at the non-recombining part of the Y chromosome have been described recently and are now widely used for the investigation of the history and the diversity of man. The tetranucleotide repeat polymorphism at the DYS389 locus consists of two repetitive stretches with different numbers of (TCTG)n (TCTA)m repeat units. To study the overall variability of this locus, 768 alleles from males from 10 human populations (two sub-Saharan African, four Caucasoid and four Asian/Amerind populations) were investigated. The alleles found in the populations of different geographic origin exhibited remarkable differences in the number and arrangement of repeats in the two repetitive stretches and up to nine different sequence variants for a single fragment length have been detected. So far 53 different alleles, i.e. haplotypes, have been observed. Analysis of molecular variance (AMOVA) indicates that at least 24.5% of the total genetic variance was found between the populations and that these differences were significant in most pairwise comparisons. We propose a model, in which both founder effects and genetic drift together with single step replication slippage mutations explain the picture of haplotype diversity observed with this single locus.

Polymorphic tetranucleotide repeat site within intron 7 of the beta-amyloid precursor protein gene and its lack of association with Alzheimer's disease.

Mutations found in the beta-amyloid precursor protein (APP) gene in a small subset of patients with Alzheimer's disease (AD) are associated with the development of the disease. Several lines of evidence indicate that specific isoforms of APP generated by alternative splicing of the primary transcript may contribute to the etiology of AD. One of the isoforms, APP695, lacks the Kunitz protease inhibitor (KPI) domain and is produced predominantly in neurons by skipping exon 7 of the APP gene. Previous studies imply that the controlling elements for exon 7 skipping exist in the flanking sequences of the exon. Therefore, we have sequenced the human intron 7 of the APP gene and found a polymorphic tetranucleotide (ATTT)n repeat site within the intron 7. In 183 genetically unrelated subjects (97 AD patients and 86 controls), we found four alleles by polymerase chain reaction (PCR) amplification of the repeat site. Although no particular alleles are associated with AD, this newly identified polymorphic site may be useful in other genetic analyses since preliminary evidence suggests allele frequency differences between African Americans and Caucasians.

Tetranucleotide repeat polymorphism at the CCSP gene.

Tetranucleotide repeat polymorphism at the CCSP gene.

No genetic association between the LRP receptor and sporadic or late-onset familial Alzheimer disease

The low-density lipoprotein receptor-related protein gene (LRP1) is often mentioned as a candidate gene for Alzheimer disease (AD) because of its role as a receptor for apolipoprotein E (apoE), a major genetic risk factor for late-onset familial and sporadic AD. A recent association study of a tetranucleotide repeat polymorphism located 5' to the LRP1 gene detected an increase in the 87 base pair allele in AD cases compared to unaffected controls. Additionally, an independent study involving a genomic screen for genes associated with late-onset AD identified a region as a possible location of a late-onset AD gene on chromosome 12p between D12S373 and D12S390, about 10 cM proximal to LRP1. We examined 144 late-onset multiplex AD families, 436 sporadic AD cases, and 240 controls and found no evidence of linkage or association of LRP1 and AD. Our data indicate that genetic variation of the LRP1 gene is not a major risk factor in the etiology of AD.

Racial differences in the distribution of a low density lipoprotein receptor-related protein (LRP) polymorphism and its association with serum lipoprotein, lipid and apolipoprotein levels

The low density lipoprotein (LDL) receptor-related protein (LRP) is a cell receptor that has close structural homology to the LDL and very low density lipoprotein receptors and thus is believed to play an important role in lipid metabolism. This study was carried out to evaluate the distribution of a known tetranucleotide repeat polymorphism in the LRP gene and its association with serum lipoprotein-lipid and apolipoprotein levels in four large samples comprising Hispanics ( n=373) and non-Hispanic Whites ( n=522) from the U.S. and Nigerian Blacks from Sokoto ( n=390) and Benin ( n=800). A total of four alleles, designated 83, 87, 91 and 95 bp, were observed. The 83 bp allele was observed at 0.4–1.1% in the two U.S. populations but was completely absent in African Blacks. Sokoto Blacks had significantly different frequencies of the 87 and 91 bp alleles compared to Hispanics ( P=0.008) and non-Hispanic Whites ( P=0.024). The frequency of the 91 bp allele was also significantly higher in Benin Blacks compared to Hispanics ( P=0.026) and non-Hispanic Whites ( P=0.054). The analysis of the relationship between the LRP polymorphism and serum lipid traits yielded some significant race and gender specific significant association for lipoprotein(a) in non-Hispanic White males ( P=0.02); HDL 2-cholesterol in Hispanic females ( P=0.03) and apolipoprotein B in Benin males ( P=0.04). We also observed an interaction between the LRP polymorphism and menopausal status for Lp(a) in Hispanic famales ( P=0.014). However, considering multiple comparisons were performed, these associations could be due to chance. Our data indicate that although the LRP tetranucleotide polymorphism exhibits inter-racial differences in its distribution, it does not appear to have a significant role in affecting serum lipid traits.